Index
A
Abscopal effect. See Bystander effects
Absolute risk.
See also Excess absolute risk
Absorbed dose
atomic bomb survivors, 20, 27, 142
and biological effect, 20
neutron weighting factor, 296-297
photon energy fluence and, 22
Activity
defined, 373
units of, 373
Acute myocardial infarction, 95
Adaptive response
animal studies, 51, 52, 53, 55, 78-79, 251
bacteria, 50
bystander effect and, 55
and cancer risk assessment, 250-251
cell cycle alterations, 51, 53
for cell lethality, 51, 52, 55, 78
in Chernobyl children, 51
to chromosomal aberrations, 51, 53, 55
cumulative effect of multiple low doses, 53
DDREF and, 78-79
to DNA damage and repair, 39, 50, 51, 52, 53, 251
dose fractionation and, 78
dose-response relationships, 45, 50-53, 62, 89
genotype and, 53
and hormesis, 333
in humans, 50
to iodine-131, 51
malignant transformation as, 51-52, 62, 78-79
in mammalian cells in vitro, 51, 52, 62
to medical uses of radiation, 51
microarray expression studies, 39, 53
modeling, 250-251
mutagenesis as, 51
to occupational exposures, 51, 53
to oxidative stress, 50
priming dose and, 51-53, 55, 78, 251
radiation resistance as, 37, 51
research needs, 53
signal transduction pathways, 51, 53
in tumorigenesis, 12, 51-52, 78-79, 250-251
variation in, 51
Additive effects, 148, 150, 297, 373
Adenine phosphoribosyltransferase, 46
Adrenal cortical carcinoma, 86, 161
Adriamycin, 130
Adult Health Study, 142, 150, 151, 153
Aflatoxins, 242
occupational exposures, 204
Alcohol consumption, 242
All-Union Distributed Registry, 202
Alpha particles
cell killing/lethality, 54
chromosome aberrations, 53
genetic susceptibility, 53, 87
and genomic instability, 70, 71
internal contamination, 199-200
LET value, 21
and leukemia, 71
and liver cancer, 68
and lung cancer, 242
RBE, 71
and tumorigenesis, 70
Amelogenesis imperfecta, 98
American Registry of Radiologic Technologists, 205
Animal studies.
See also specific animals
bone cancer, 74
breast/mammary cancer, 74, 82, 83, 88
DNA damage and repair mechanisms, 34, 36, 42, 52, 69, 71
dose-response relationships, 73-75, 89, 245
extrapolation to humans, 73, 96-98, 109-111, 114, 115
genetic effects of radiation, 12, 68-70, 73, 82-83, 92, 96-97
genetic susceptibility to cancer, 68-70, 71, 73, 82-83, 87-88, 89
of growth and developmental effects, 115
of hormesis, 334
leukemia, 68-70, 71, 72, 73-74, 87
life-shortening effects of radiation, 246
limitations of, 245
lung cancer, 28, 50, 74, 76, 87
radiosensitivity, 34, 69, 71, 82-83
tumorigenesis, radiation-induced, 11, 12, 67, 68-70, 73-79, 82-83, 89, 240, 241, 246
X-ray exposure, 68, 69, 100-101
Aniridia, 98
Ankylosing spondylitis cohorts
bone cancer, 164
breast cancer, 164-165, 176, 177
cohort description, 164
colon cancer, 164
esophageal cancer, 164
kidney cancer, 164
malignant lymphoma, 164
modeling cancer risk in, 287
multiple myeloma, 164
pancreatic cancer, 164
radiotherapy-related cancer risks, 164-165, 174, 176, 177, 185, 287, 288, 289
Antibody genes, 34
Antitumorigenic defenses, 67
Aplastic anemia, 153
Apoptosis, 48-49, 54, 55, 67, 80, 81, 88, 373
Apurinic-apyrimidinic endonuclease (APE1), 32, 33
Arthroses, 165
Asbestos, 200
Ashkenazi Jews, 85
Ataxia telangiectasia, 35, 36, 79, 80, 81, 82, 83, 86, 93
ATF3, 56
ATM kinase, 35, 36, 37, 39, 50, 56
Atomic Bomb Casualty Commission, 91, 141
Atomic bomb survivors
Adult Health Study, 142, 150, 151, 153
age and cancer risks, 72, 143, 144, 145, 147, 148, 149, 240, 297-298
benign neoplasms, 150, 151-152
bladder cancer, 147, 148, 269, 303-306
bone cancer, 269
breast cancer, 12, 26, 85, 135, 147, 148-149, 170, 177, 180, 243, 269, 303-306
cancer risk assessment, 7-8, 138, 143-154, 239-240, 241-245, 262, 275-276, 285-286, 296-308
cardiovascular disease and stroke, 1, 8, 152, 153, 185
cataracts, 153
children of, 6, 8-9, 114, 118, 129, 130-131, 149, 151
chromosome nondisjunctions, 131
cohort description, 13, 141, 142-143
colon cancer, 147, 148, 149, 151, 269, 303-306
compatibility of data with other cohorts, 267-268
Committee’s analysis of data, 267-268, 296-308
confounding and bias in studies, 141, 146, 152-153, 268, 297
cytogenetic studies, 68
data used in this study, 13, 142, 144
deaths from cancer, 142, 143, 144, 145, 147, 151
digestive system cancers, 149
dose-response relationships, 6, 13, 24, 45, 68, 72, 137, 140, 142, 143, 144, 145-146, 147, 149, 150, 151, 152, 153, 245
dosimetry, 6, 9, 10, 20, 24, 27, 72, 129, 134, 139, 141, 142-143, 144, 266
doubling dose, 7, 8, 118, 124, 130-131, 252
DREF, 146
esophageal cancer, 147, 148, 149, 215, 269
extrapolation to low dose rates, 146
follow-up, 8, 134, 239-240, 245
gall bladder cancer, 147, 148, 149, 269
genetic risk assessment, 8-9, 91, 92, 114, 115, 118, 131, 252
health end point data, 13, 76-77, 130, 131, 142
healthy survivor effect, 152
incidence of cancer, 13, 130, 142, 144-145, 148-149, 151, 298-307
infant and childhood mortality, 8
leukemia, 68, 72, 142, 143, 144, 153, 172, 240, 244, 245, 269, 307-308
life shortening, 153-154
Life Span Study, 9, 12-13, 26, 141-154, 239-240, 242, 245, 246-250, 267-268, 296-308
limitations of studies, 141, 240
liver cancer, 147, 150, 148, 149, 242, 269, 303-306
lung cancer, 68, 147, 148, 150, 215, 242, 269, 276, 303-306
medical exposure data combined with, 146-147
mental retardation, 1
mortality data, 130, 131, 141, 142, 143, 144, 145, 147, 151, 152-153, 298-307
multiple myeloma, 151
mutation rates, 6, 114, 129, 130-131
nervous system cancers, 148, 149, 151, 152
neutron RBE, 20, 27, 142, 143, 146
nonneoplastic disease, 13, 143, 152-153
nuclear industry workers compared, 201, 203
oropharyngeal cancers, 148, 149
ovarian cancer, 147, 148, 149, 269, 303-306
pancreatic cancer, 147, 148, 149
prostate cancer, 147, 148, 149, 303-306
respiratory system cancers, 149
salivary gland cancer, 149-150, 269
sex differences, 144, 145, 150, 151, 153
site-specific cancers, 147-151, 303-307
skin cancers, 148, 149, 150-151, 269, 295
solid cancers, 13, 45, 130, 142, 143, 144-147, 149, 245, 297-305
statistical analyses, 143-144
stomach cancer, 147, 148, 149, 150, 173-174, 215, 240, 242, 269, 303-306
suicides, 153
thyroid cancer, 148, 149, 181, 269, 295
transport of risks to other populations, 14, 240, 241-245, 267-268, 275-276
two-stage clonal expansion model applied to, 262
uncertainties in data, 130, 131, 141, 147, 172, 285-286
urinary tract cancer, 148, 149
uterine cancer, 147, 148, 149, 303-306
Atomic Energy Authority (UK), 190, 191, 192, 195, 196, 197, 198, 199, 232, 233
Atomic Energy of Canada Ltd., 191, 192, 195, 196, 197, 199
Atomic Weapons Establishment (UK), 190, 191, 192, 194, 195, 196, 197-198, 232, 233
Attributable risk, defined, 373
Autoimmune diseases, 225
Autoimmune hypothyroidism, 151
Autopsy data
atomic bomb survivors, 151, 152, 153
noncancer diseases, 151, 152, 153
B
Background radiation. See Natural background radiation
Bacteria
adaptive response, 50
tumor promotion, 241-242
Basal cell carcinoma, 66, 68, 69, 80, 84, 150-151, 167.
See also Skin cancer
BAX, 56
Bcl2, 49
BEAR report
doubling dose method for humans, 96, 123
Becquerel, Henri, 2
BEIR I report
doubling dose method for humans, 96, 97, 118, 122, 123
genetic effects estimation, 94
principles of risk estimation, 138
BEIR III report
cancer risk models, 138
doubling dose method for humans, 118, 122-124
genetic risk estimates, 94, 94-95
advances in risk estimates since, 115-116, 187
baseline frequencies of genetic diseases, 94-95, 96, 115, 117-118
cancer risk assessment, 138, 174, 187, 246, 265, 275, 282, 283, 291-292, 299
dose-rate reduction factor, 100 n.1, 246
doubling dose calculation, 94-96, 100 n.1, 115, 118, 123, 124, 252
environmental exposure studies, 208, 209-214
extrapolation of animal data to humans, 115
genetic disease risk estimates, 12, 94-95, 96, 115-116, 117-118, 252
multifactorial disease estimates, 95, 96, 115, 117
mutation component, 94, 106, 115
occupational exposure studies, 190
Benign diseases.
See also Ankylosing spondylitis cohorts;
Thyroid diseases;
Tinea capitis cohorts;
other specific diseases
age at exposure and, 151
in atomic bomb survivors, 150, 151-152
breast disease, 26, 151, 163, 174, 177, 180, 185, 287
in children, 26, 68, 155, 156, 166-170, 174, 176, 177, 180, 181, 182, 183
dose-response relationship, 151
genetic susceptibility, 80
hormonal infertility, 164
radiotherapy effects, 155, 162-167, 181, 289
salivary tumors, 150
skin hemangiomas, 26, 168-169, 174, 175, 176, 177, 180, 181, 183, 185
thymus gland enlargement, 26, 167-168, 176, 177, 180, 181, 182
tonsil enlargement, 169
uterine bleeding, 163-164, 183
Beryllium, 200
Best’s macular dystrophy, 125
Beta particles
defined, 373
skin cancer in mice, 75
Bias.
See also Confounding factors;
Uncertainties
assessment of, 139
DDREF estimate, 250
defined, 373
in epidemiological studies, 132, 133, 135-136, 139, 140, 152, 173, 187, 208
information, 135-136, 139, 208, 276
misclassification of disease, 139, 152-153, 285
misclassification of exposure, 139, 207, 266, 285
random errors, 296
reduction strategies, 140
selection, 135, 139, 152, 203, 208
underascertainment or misclassification of cancer incidence, 285
Biological damage. See Chromosome aberrations;
DNA damage;
Genetic effects of radiation;
Relative biological effectiveness
critical sites, 27, 29, 47, 48, 54, 74
process during energy transfer, 20, 245
responses to, 11;
see also DNA repair mechanisms and defects;
Tumorigenesis, radiation induced
Bladder cancer.
See also Urinary tract cancer
in atomic bomb survivors, 147, 148, 298, 303-306
radiotherapy-related, 157, 158, 162, 163, 164
risk models and estimates, 272, 278, 279, 280, 282, 284, 285, 294, 303-306
Bleomycin, 130
Blindness, 98
Bloom’s syndrome, 93
Bone cancer
age factors and, 264
animal studies, 74
ankylosing spondylitis cohort, 164
in cervical cancer survivors, 157
childhood exposure and, 161, 167
dose-response relationship, 74, 75, 201, 264
genetic susceptibility, 80, 84
high-LET radiation and, 87, 269
human data, 84
in nuclear industry workers, 201
protracted exposure and, 75
radiotherapy-related risks, 157, 161, 162, 164, 167
risk models and estimates, 269, 282, 294
Bone marrow cells, 71, 72, 74, 80, 173
Bowen’s disease, 151
Brachytherapy, 162
Brain tumors, 80, 162, 164, 166, 167, 168, 169, 218
Brca1 protein, 35, 36, 37, 38, 39
Breakage-fusion-bridge (B/F/B) cycles, 48, 71
Breast cancer, female
additive risk, 148
age at exposure and, 26, 147, 149, 160, 167, 170, 176, 180
age-specific rates, 149
animal studies, 74, 82, 83, 88;
see also Mammary cancer;
specific animals
in ankylosing spondylitis cohort, 164-165, 176, 177
in atomic bomb survivors, 12, 26, 85, 135, 147, 148-149, 170, 177, 180, 243, 269, 287
baseline lifetime risk estimates, 278
BEIR V model, 291-292
in benign breast disease cohorts, 26, 163, 177, 180, 243, 287
BRCA-type heritable, 67, 79, 80, 82, 83, 84, 85-86, 243
cardiovascular disease mortality, 186-187
in cervical cancer survivors, 26, 157-158, 176, 177
chemotherapy and, 159
Chernobyl accident and, 227
childhood exposures to radiation and, 26, 167, 168, 169, 172, 175, 176, 177, 180, 243, 287
chromosomal radiosensitivity and, 86
cobalt-60 irradiation, 186-187
coherence of BEIR VII model with other studies, 287
contralateral, in radiotherapy recipients, 160
diagnostic irradiation and, 170, 172, 176, 177, 287
dose fractionation and, 26, 170, 176-177
dose-response relationships, 74, 76, 86, 149, 157-158, 159, 160, 163, 168, 170, 172, 176, 178-180
epidemiological studies, 24-26, 157, 287
etiology, 243
excess absolute risk, 12, 25, 26, 149, 168, 243, 287, 305, 306
excess relative risk, 12, 25, 26, 148, 149, 159, 164, 175, 240, 242, 243, 244, 303, 304
in fluoroscopy cohorts, 26, 170, 176, 177, 180, 243, 287, 293
genetic susceptibility, 67, 79, 80, 82, 83, 84, 85-86, 87-88, 103, 243
in Hodgkin’s disease survivors, 158, 159, 176, 177
hormonal/reproductive factors, 76, 157-158, 159, 168, 169, 241, 243
hypersensitivity to radiation and, 56, 82
incidence, 148-149, 176, 177, 243, 278, 279, 280, 298, 303, 305
LET of radiation and, 24-26
leukemia in radiotherapy recipients, 159-160
lung cancer in radiotherapy recipients, 160, 174, 175
in mastitis treatment group, 26, 163, 177, 180, 287
MCF-7:W58 cell lines, 56
medical-exposure-related risks, 12, 26, 84, 86, 157, 160, 163, 176-180, 286, 287
mortality, 170, 172, 176, 177, 243, 278, 279, 280, 287, 298
multiplicative model, 148, 163, 243
pooled analyses of data, 12, 169, 180, 243, 268-269, 287
protracted exposure and, 176, 180, 243
in radiologic technologists, 205
radiotherapy-related risks, 26, 84, 86, 157, 159-160, 164-165, 167, 168, 169, 174, 175, 176, 177, 186-187, 205, 243, 287
risk assessment, 25-26, 85-86, 148-149, 176-180, 241, 243, 244, 272, 273, 275, 286, 287, 293, 303-306
risk estimates, 173, 176-180, 278, 279, 280, 282, 294
uncertainties in risk models, 25-26, 285
British Nuclear Fuels, 232, 233
Bromodeoxyuridine (BrdU), 48, 60-61
bub1, 39
Building materials, 3
Bystander effects, 9, 11, 29, 37, 39, 45, 53-55, 62, 70, 251
C
c-fos transcription factor, 51, 53
c-jun N-terminal kinase (JNK), 55
c-jun transcription factor, 51, 53
Californium-252, 113
Canadian fluoroscopy study, 176
Canadian National Dose Registry, 190-191, 192, 194, 195, 196, 198, 199, 230, 262
Canadian National Mortality Data Base, 198
Canadian nuclear workers, 192-193, 195, 196, 197
Cancer.
See also Carcinogenesis;
Genetic susceptibility to cancer;
Tumorigenesis, radiation induced;
specific sites
age (attained) and incidence of, 72, 143, 144, 145, 148, 149, 167-168, 180-181
age at exposure and, 7, 26, 74, 76, 86, 143, 147, 149, 150, 160, 167, 170, 176, 180, 181-182, 311
apoptosis and, 49
in childhood following in utero exposure, 1, 6, 10, 112, 151, 172-173, 211, 226
data availability, 6
defined, 373
genes, 12, 67, 79, 80, 82, 83, 84, 85-86, 243;
see also Oncogenes
incidence, 73, 130, 142, 144-145, 148-149, 151, 194-198, 200, 201, 202, 203, 298-307
inherited predisposition, see Genetic susceptibility to cancer
metastatic, 150
misclassification of disease status, 139
mortality/life shortening, 2, 4-5, 28-29, 68, 76-77, 142, 144, 145, 151, 165, 170, 172, 174, 175, 176, 177, 181, 189, 191, 194-198, 200, 201, 202, 203, 204, 205, 209-212, 242, 243, 298-307
multifactorial nature of, 81, 88
multistep process, 75, 240, 241
registries, 13, 141, 142, 147-148, 150, 151, 152, 160, 166, 202, 203, 205, 226, 268
sex differences, 7, 73, 74, 144, 145, 150, 151, 161, 167, 176, 181, 244
Cancer cells.
See also Cell cultures;
In vitro assays
Cancer patients. See Radiotherapy studies
Cancer risk assessment.
See also Atomic bomb survivors;
Excess absolute risk;
Excess relative risk;
Linear no-threshold model;
Linear-quadratic model;
Model fitting;
Models/modeling;
Risk assessment;
specific cancer sites
absolute risk model, 242, 244, 245, 253-254, 268, 279-281, 283
adaptive response and, 250-251
additive model, 148, 150, 240, 241, 244-245, 254, 276
age dependencies, 143, 144-145, 147, 148, 149, 240, 262, 268, 269, 270, 271, 273, 274, 275, 278, 284, 285, 286, 296, 297-298, 311
alternative models, 271, 285-286, 298-302
analytical approach, 269, 296-302
atomic bomb survivors, 7-8, 12-13, 138, 143-154, 239-240, 241-245, 267-276, 285-286, 296-308
baseline incidence and mortality data, 268, 275, 278, 373
BEIR III estimates, 138
BEIR V estimates, 138, 174, 187, 265, 268, 275, 277, 282-283, 291-292, 299
biologically based models, 241, 245, 262-263
for bone cancer, 269
breast cancer (female), 25-26, 85-86, 148-149, 163, 176-180, 241, 243, 244, 268, 272, 273, 275, 282, 286, 287
bystander effects and, 251
calculation of lifetime risk, 264-265, 266, 277-278, 284-286, 310-312
for children, 10, 26, 161-162, 166-170, 181, 209
comparability of study designs and, 241
comparison of BEIR VII estimates with other sources, 282-284, 291-296
confidence intervals, 14, 278, 279, 284, 286, 296, 299, 309
data used for BEIR VIII model, 267-268, 277, 283-284, 296-308
DDREF adjustment, 246-250, 254-258, 274, 275-276, 279, 280, 282, 283, 284, 285, 286
dose-response functions, 245-246, 262, 269, 274, 280, 298
dosimetry and, 241, 266, 268, 269, 285, 286, 296
DREF, 146
endpoints, 268-269
EPA estimates, 274, 275, 282-283, 293
estimates of lifetime risk, 145, 278-286
etiology at different histologic sites and, 241-245
examples of estimates, 310-312
extrapolation from high to low doses, 50, 146
genetic susceptibility and, 85-87, 88, 241, 251
genomic instability and, 251
human data for;
see Epidemiological studies;
Human cell lines/systems;
Human studies
ICRP estimates, 274, 282-283, 292-293
incidence data, 146, 268, 270, 271, 272, 273, 278, 279, 280, 281, 283, 284, 298-302, 311, 312
internal exposure and, 276
latent period, 302
for leukemia, 143, 144, 173, 183-185, 244, 245, 246, 268, 273-274, 275, 277, 278, 280-282, 289-290, 307-308, 309
lifetime attributable risk, 277-286, 309-312
liver cancer, 242, 272, 278, 279, 280, 282
lung cancer, 147, 148, 173, 174-176, 242, 244-245, 272, 275, 278, 279, 280, 282, 286
measures of risk, 268-269, 277
medical uses of radiation, 12, 26, 173-187, 240, 241, 276, 286-290
method of calculating lifetime risk, 277-278
model selection for this study, 6-8, 138, 269-274
modifying factors and, 240, 268-269
mortality data, 144-145, 268, 273, 275, 278, 280, 281, 282, 283, 298-302, 311, 312
multiplicative model, 148, 163, 240, 241, 242, 243, 254, 292
NCRP review of models, 274, 293
neutron RBE and, 28-29
NIH model, 268, 269, 273, 277-278, 293, 294-296, 299
nuclear industry workers, 138, 262, 268, 275, 290
parameter estimates, 268, 278, 279, 280, 284, 285, 308-309
pooled analyses of data, 169, 180, 181, 243, 268-269, 273, 286
population modeling, 85, 88, 286
postirradiation cancer mechanisms and, 241
preferred (BEIR VII) model, 244, 269-278, 296-312
probability of causation in, 265, 294
REID measure, 277
relative risk model, 25, 26, 148, 149, 159, 164, 175, 240, 242, 243, 244, 253, 279-281, 283, 307
RERF model, 269, 270, 271, 285, 286, 296, 298, 297, 301, 302, 307
results of calculations, 278-284
Rochester thymus cohort, 26, 180, 181, 273, 292
sex-specific, 267, 271, 274, 275, 278-281, 282-283, 284, 298, 301, 311, 312
site-specific, 88, 241-242, 268-269, 272-273, 275, 278, 282, 283, 284, 285, 292, 303-307, 311, 312
skin cancer, 245, 270-271, 282, 294, 295
solid cancers (all), 144-145, 268-273, 278, 279-280, 281, 282, 284, 287-289, 296, 297-302, 312
stratified-background relative risk model, 299
temporal projections, 239-240, 275
threshold models, 12, 74-75, 105-108, 120-121, 124
thyroid cancer, 181, 244, 268, 270-271, 272, 273, 275, 282, 286, 287
time since exposure, 271, 274, 275, 289, 296
tonsil irradiation cohort, 273
transport between different populations, 85, 88, 240-245, 253-254, 265, 275-276, 277, 278-281, 284, 285, 286, 292
uncertainties in, 25-26, 147, 174, 241, 244, 251, 268, 272-273, 275, 276, 278, 279, 280, 284-286, 297, 308-310
UNSCEAR approach, 138, 240, 268, 272, 274, 275, 277-278, 282-283, 293-294, 297-298, 307
for U.S. population, 274-284, 286
Capenhurst nuclear workers, 191, 192, 195, 196
Carbon-14, 3
Carcinogenesis.
See also Tumorigenesis, radiation induced
age and, 262
Armitage-Doll model, 262
bystander effects and, 9, 29, 54
cell cycle effects, 49, 50, 86
frequency, 52
general mutagen model, 262
genetics of, see Genetic susceptibility to cancer
latent damage, 65, 68, 72, 76, 78, 159, 167, 215
LET of radiation and, 24-26, 49
malignant transformation, 51-52, 62, 78-79, 262
mathematical theory of, 262
modifiers of, 200-201
protooncogenes, 66, 68, 80, 81-82
repair of injury, 76
smoking and, 242
two-stage clonal expansion model, 241, 253-254, 262
Carcinogens
chemical, 244
defined, 373
and genetic polymorphism, 87
Cardiovascular disease, 8
in atomic bomb survivors, 1, 8, 152, 153, 185
in breast cancer survivors, 186-187
dose-response relationships, 152, 153
medical-exposure-related risks, 12, 159, 160, 163, 185-187
occupational exposures and, 199
Case control studies, 84, 133, 134-135, 136, 148, 172, 173, 190, 207, 208.
See also Epidemiological studies;
individual cohorts
Chernobyl accident, 224, 225, 226
defined, 373
environmental radiation exposures, 211-212, 224-225, 229, 230, 233, 235
Casein kinase I and II, 39
Caspase cleavage, 49
Cataracts (early onset), 28, 98, 112, 115, 116, 153
Cell cultures.
See also Human cell lines;
In vitro assays;
Lymphocytes systems;
individual animal cell lines
defined, 373
Cell cycle phase
and carcinogenesis, 49, 50, 86
and cellular response, 45, 49-50
checkpoint kinase gene, 86
and chromosome aberrations, 45, 46, 48, 49, 82
and DNA repair, 34, 37, 39, 48-49, 50, 245-246
dose-response relationship, 45, 50
and genomic instability, 49, 113
and mutagenesis, 49, 50, 81, 113
and neutron RBE, 50
and radiosensitivity, 45, 49-50, 55, 82, 83, 86, 113
regulator protein, 39
and translocations, 45
Cell cyclin proteins, 52
Cell killing/lethality.
See also Apoptosis
adaptive response, 51, 52, 55, 78
by alpha particles, 54
bystander effects, 9, 29, 54-55
chemical modification of radiation effects, 31
delayed, 55
DNA damage response disorders and, 82
dose-response relationships, 55-57, 75, 78
gene mutation and, 47
hypersensitivity to radiation and, 55-57
by low-LET radiation, 55-57
by neutrons, 28
oocyte sensitivity, 75, 98-99, 119
in radiotherapy patients, 155
signal, 56
and tumorigenesis, 12, 74, 75, 76, 82
Cell senescence, 72
Cellular response.
See also Adaptive response;
Cell killing/lethality;
Chromosome aberrations;
Genomic instability, radiation induced;
Germ cells;
Somatic cells
bystander effects, 9, 29, 37, 39, 47, 53-55
hypersensitivity to radiation, 11, 32, 45, 47, 51, 55-57, 82
membrane damage, 29
multilocus mutations, 46
Central nervous system cancers, 151, 161, 166-167, 168-169
Cerebrovascular injury, 185
Cervical cancer survivors
bone cancer, 157
breast cancer risk, 26, 157-158, 176, 177
dosimetry for radiotherapy, 26, 157
leukemia in, 157, 158, 183, 289
lung cancer, 157
lymphoma, 157
rectal carcinoma, 157
risk estimates, 287
secondary cancers in radiotherapy cohort, 26, 135, 157-158, 174, 176, 177, 185
thyroid cancer, 181
urinary tract cancer, 157, 158
uterine cancer, 157
Cervical polyps, 153
Cervical tubercular adenitis, 169
Cesium-137, 114, 128, 202, 212, 213, 214, 215-226, 276
Chalk River plant, 191
Chapelcross nuclear workers, 191
Chemical aspects of radiation
background radiation, 30-31
DNA damage mechanisms, 29-30
electron ionization of water, 20, 21, 29-30
in locally multiply damaged sites, 31-32
oxidation reactions, 30, 31-32, 40-42, 48, 50, 54
spontaneous DNA damage, 29-30
Chemotherapy, additive effects of, 159, 244
Chernobyl accident
adaptive response in children, 51
brain cancer, 218
breast cancer, 227
case control studies, 224, 225, 226
childhood cancers, 51, 68, 72, 114, 128, 215-226, 227, 235, 246
chromosome aberrations, 57
cleanup (liquidation) workers, 57, 58, 60, 114, 129, 202-204, 226, 227
congenital abnormalities, 218
DNA damage repair indicators, 222, 228
dose-response relationships, 224, 225, 226-227
dosimetry, 114, 128, 129, 202, 203, 216-223, 224
Down’s syndrome, 216
ecologic studies, 215, 216-223, 226
environmental exposures, 215-228, 234-235, 236
follow-up, 202-203
gastrointestinal cancers, 218
goiter, 218
human minisatellite loci mutations, 128-129
internal exposures, 276
leukemia, 203-204, 216-222, 225-227
mutation rates, 114, 128, 129-130
population exposures, 114, 202, 215-228
renal cell carcinoma, 222
respiratory tract cancers, 218
risk estimates, 203-204
solid tumors (nonthyroid), 227-228
thyroid cancer, 68, 72, 203-204, 215-226, 234-235, 246, 276
uncertainty in data, 128, 129, 202-203
urinary bladder cancer, 223, 227-228
Chernobyl Registry, 202
Children/childhood.
See also Postradiation generation progeny
of atomic bomb survivors, 6, 8-9, 114, 118, 129, 130-131, 149, 151
benign diseases, 26, 68, 155, 156, 166-170, 174, 176, 177, 180, 181, 182, 183
brain and central nervous system tumors, 161, 166-167, 168-169
breast cancer in women exposed during, 26, 167, 168, 169, 172, 175, 176, 177, 180, 243
cancer risk estimates, 10, 26, 161-162, 166-170, 181, 209
Chernobyl, 51, 68, 72, 114, 128, 215-226, 227, 235, 246
CT scans, 172-173
cytogenetic study, 68
descriptive studies, 208
diagnostic exposures, 155, 156, 172-173, 211
dose-response relationships, 10, 161, 162, 168, 169
doubling doses in, 130-131
endocrine gland tumors, 168
environmental exposures, 208, 209-210, 211, 212, 213, 215-226, 229, 233, 234, 235-238
genetic effects of radiation, 8-9, 68, 114, 118, 161
in utero radiation exposure, 1, 6, 10, 112, 151, 172-173, 211, 226
infants, 167-168, 175, 211, 218, 226, 287
iodine-131 exposure, 68, 169, 173, 215
leukemia, 84, 161, 168, 172, 209, 210, 211, 212, 214, 216-222, 226-227, 233, 244
melanoma, 161
mental retardation, 1
mutation frequencies, 114, 128, 130-131
pancreatic cancer, 168
parental preconception exposures, 8-9, 114, 130-131, 175, 214, 228-233
radiotherapy-related risks, 9, 84, 161-162, 166-170
retinoblastoma, 161
salivary gland tumors, 167
skin hemangioma cohort, 26, 168-169, 172, 174, 175, 176, 177, 178, 180, 181, 183, 185, 287
soft tissue sarcoma, 161
thymus radiography cohort, 26, 167-168, 176, 177, 180, 181, 182, 243, 287, 292
thyroid cancer, 68, 72, 149, 161, 162, 166, 167, 168, 169, 181, 182, 214, 215-226, 234, 244, 246, 287
thyroid diseases, 169
tonsil enlargement, 169
X-ray exposures, 211
Cholangiocarcinomas, 150
Chromatid instability
in hematopoietic cells, 70-71, 86
in mouse mammary epithelial cells, 71-73
Chromatin remodeling, 69
Chromium-51, 200
Chromosomal diseases, 93, 96, 117, 119
Chromosome aberrations
alpha particles and, 53
aneuploidy, 48, 49, 69, 70, 83, 130, 131
breaks, 51
and breast cancer, 86
bridge formations, 45, 47, 48, 71
cell cycle stage and, 45, 46, 48, 49, 82
Chernobyl accident and, 57
and colon cancer risk, 86
complex exchanges, 46, 48, 67, 68
delayed, 54
deletions, 29, 30, 35, 46, 68, 69, 93
dicentric exchanges, 24, 25, 28, 45, 46, 57, 58, 71
diseases arising from, 82, 93, 96
DNA repair defects and, 45-46, 57, 65
dose fraction and, 57
dose-response relationship, 24, 25, 45-46, 57-59, 60-61, 73, 74, 256, 257
and genomic instability, 46, 47-48, 49, 54, 58, 59, 60-61, 70, 251
gross loss events, 66
heritable fragile sites, 69
in human lymphocytes, 24, 25, 28, 45, 46, 51, 53, 57, 58, 59, 61, 86
inversions, 48
late effects, 24
LET dependence, 45
in mammalian cells, 45
in mammary epithelial cells, 61, 71
mechanisms of induction, 45-46, 74
microsatellite sequence instability, 68, 72
monocentric exchanges, 45;
see also Translocations
neutron RBE and, 28
nondisjunctions, 131
in plant cells, 45
proximity effects, 45
rate of formation, 46
saturation effects at high doses, 45
spontaneous, 53
telomere-associated instability, 71-73
trisomy, 93
and tumorigenesis, 24, 46, 48, 66, 68-69, 70, 72-73, 74, 82, 86
Chromosomes
basic concepts, 327
human, 5, 11, 21, 58, 59, 61, 93
Cigarette smoking. See Smokers/smoking
Coal-fired power plant emissions, 3
Cobalt-60
breast cancer and, 186-187
chromosome aberrations, 57
and heart disease mortality in breast cancer survivors, 186-187
LET value for electrons, 19 n.1, 21, 22, 24, 276
occupational exposure, 200
Cockaynes syndrome, 80
See also Atomic bomb survivors;
Radiotherapy studies
Colon cancer
in atomic bomb survivors, 147, 148, 149, 151, 269, 303-306
baseline lifetime risk estimates, 278
chromosome aberrations and, 86
genetic susceptibility, 66, 67, 79, 80, 86-87
hereditary nonpolyposis, 79
incidence, 278, 279, 284, 298, 303, 305
mortality, 278, 280, 282, 298, 304, 306
in radiologists and radiologic technologists, 205
in radiotherapy recipients, 163, 164, 288
risk models and estimates, 272, 275, 278-280, 282, 284, 287, 288, 294, 303-306
Colorectal cancer, 80, 82, 161
Combined UK Industrial Workforce study, 200
Committee of the British Medical Research Council, 91
Computed tomography (CT) scans, 4-5, 156
Computer monitors, 3
Confounding factors
in atomic bomb survivor studies, 141, 146, 152-153, 268, 297
birth cohort effects, 297, 302
chemical exposures, 233
control of, 138
country differences in baseline cancer rates, 268
defined, 133
in ecologic studies, 207
healthy worker/survivor effect, 136, 152, 189, 194, 205
lifestyle-related, 57, 138, 198, 199, 240
occupational exposures, 136, 189, 194, 198, 199-200, 205
socioeconomic status, 198
species variation in susceptibility, 73
stress, 71
Congenital disorders
Chernobyl accident and, 218
doubling dose, 131
environmental radiation exposures and, 211, 229, 230, 232, 233, 235
frequencies, 112
multifactorial nature of, 93, 95, 96, 112, 117
mutation component, 105-106, 111, 116
PRCF, 111
risk estimates, 115, 116, 117, 120
Consumer product radiation, U.S. population exposure to, 3, 5
Contiguous gene deletion syndromes, 112
Cooperative Thyrotoxicosis Therapy Follow-up Study, 165, 166
Coronary heart disease, 81, 93, 106, 111
Cosmic radiation, 3, 4, 30, 43, 204
Cri du chat syndrome, 93
Crouzon’s syndrome, 103
CS-A, CS-B genes, 80
Cumene hydroperoxide, 40
Curie, Marie and Pierre, 2
Cyclin B1, 53
Cyclin-dependent protein kinase catalytic subunit, 127
Cyclodeoxynucleosides, nucleotide-excision repair, 32, 34-35
Cyclophosphamide, 130
Cytochrome c, 49
Cytogenetic studies, 68
Cytokines, 54
D
Dally, Clarence, 2
Danish Cancer Registry, 160, 205
Deaf mutism, 98
Death certificates, reliability of data from, 142, 150, 152-153, 208, 303
Defense Radiological Protection Service (British), 190
Delayed lethality, 47
Dementia, 153
Dental radiography, 156
Dentinogenesis imperfecta, 98
Denys Drash syndrome, 80
Development. See Growth and Development effects
Diabetes mellitus, 8, 93, 111, 113
Diagnostic radiography.
See also Medical uses of radiation
adults, 170-172
angiography, 156
and breast cancer, 170, 172, 176, 177
cancer mortality risk, 4-5, 68, 170, 176
children, 155, 156, 172-173, 211
cumulative doses, 156
fluoroscopy for pulmonary tuberculosis follow-up, 155, 170-171, 174, 175, 176, 177, 187
in utero exposures, 172-173
interventional procedures, 156
iodine-131 exposures, 171, 173, 234
limitations of studies, 187
and liver tumors, 68
and lung cancer, 170, 174, 176
and lymphoma, 171
mammography, 4, 20, 21, 22, 24
photon energies, 20
radioisotope studies, 156
techniques, 156
uncertainties in risk estimates, 286
X-rays, 3, 4, 5, 6, 21, 22, 156, 171, 286
Digestive system cancer.
See also Colon cancer;
Esophageal cancer;
Rectal cancer;
Stomach cancer
in atomic bomb survivors, 149
risk estimates compared, 282, 292, 294
secondary, in radiotherapy patients, 159
DNA amplification, 48
DNA-binding proteins, 34
DNA damage
adaptive response to, 39, 50, 51, 52, 53
base removal, destruction, or mutation, 29, 30, 31, 32, 46, 54
and cancer risk, 239
chemically induced, 34-35
Chernobyl accident and, 222, 228
and chromosome aberrations, 45
dose-response relationship, 31, 73, 246-247
double strand breaks, 29, 30, 31, 45-46, 48, 52, 65, 70, 73, 245
free radicals and, 19, 29-30, 239
internucleosomal digestion of DNA, 49
LET of radiation and, 26-27, 31, 62
locally multiply damaged sites (clustered damage), 26-27, 31-32, 34, 46, 48
low vs high dose and, 9-10, 31, 45, 46
measurement, 31
mechanisms, 29-30, 26-27, 29-32, 62
natural background radiation and, 30-31
oxidative, 19, 30-32, 34, 40-42, 50
probability from energetic electrons, 26-27
protracted, low-dose exposure and, 31
proximity-promoted interaction of lesions, 45
and radiosensitivity, 32, 34, 37, 56
resonance phenomenon, 29-30
signaling presence of, 36, 50, 65
single-strand breaks, 29, 30, 31
spontaneous vs. induced, 30, 31, 34
strand invasion, 38
time dependence, 46
track characteristics and, 10, 45
DNA-DNA covalent cross-links, 30
DNA-membrane complex, 29
DNA-protein covalent cross-links, 30
DNA radical, 29
DNA repair mechanisms and defects
animal studies, 34, 36, 42, 52, 69, 71
base-excision, 32-34, 51, 53, 80, 87
bystander effect, 54
cell cycle phases and, 34, 37, 39, 48-49, 50, 245-246
and cell lethality, 82
in chick cells, 36
and chromosomal aberrations, 45-46, 57, 65
of cyclodeoxynucleosides, 34-35
of double-strand breaks, 32, 34-35, 36-39, 42, 45-46, 47, 49, 51, 65, 73, 81, 87
fast reaction, 35-36
and gene amplification, 47
genes, 36, 37, 39, 40, 42, 71, 86, 87-88
and genetic susceptibility to cancer, 71, 79-81, 87
and genome instability, 48, 49, 72
and growth and development, 34
homeologous recombination, 36, 245-246
homologous recombination, 32, 35, 36, 38, 49
hypersensitivity to radiation and, 56, 71, 239
inducible, 36-39
of locally multiply damaged sites, 27, 31, 34, 35, 36
loss-of-function mutations, 67
microhomology-mediated, 38
molecular mechanisms, 32-39
nonhomologous end joining, 29, 32, 35-36, 40, 42, 46, 47, 48, 68, 70, 71, 80, 87, 245
normal processes, 32
nucleotide-excision, 32, 34-35, 87
oxidative processes and, 31-32, 40-42, 48
radiation resistance and, 49
and radiosensitivity, 32, 34, 37, 40, 56, 69, 71, 80, 82, 83, 87, 239
of refractory, complex breaks, 35, 36
signal transduction pathways, 32, 34, 36-39, 48, 49, 54, 80
of single-strand breaks, 32, 34, 56, 80
in somatic cells, 36
spontaneous vs. induced damaged, 31, 34
track of radiation and, 10, 43-44
and tumorigenesis, 6, 11, 65, 68, 69, 70, 73, 82, 83, 227-228, 239, 246
xeroderma pigmentosum patients, 79, 80, 81
Dogs, life-span shortening, 76
Dose.
See also Absorbed dose;
Effective dose;
Equivalent dose, defined;
Low doses
combining low- and high-LET radiations, 2, 3, 199
conversion factors, xi
defined, 374
estimating, 137, 166, 203, 207, 266;
see also Dosimetry of ionizing radiation
extrapolation of high to low, 9, 29, 44, 50, 54, 62, 146, 296
of internally deposited radionuclides, 3, 4
linear-quadratic function, 143
population, 207
skin erythema, 2
variability within populations, 207
weighting factor, xi, 142, 143, 204, 275-276, 378
Dose and dose-rate effectiveness factor (DDREF)
for acute doses, 60
adaptive response and, 78-79
from animal studies, 77-79, 246, 254-258
for atomic bomb survivors, 246-250, 254-258
bias and variance of sample estimate of, 250
cancer risk assessment, 246-250, 254-258, 274-278, 282, 309
from cellular and molecular studies, 246, 256
derivation by Bayesian analysis, 246-250, 254-258
and dose-response relationship, 44-45, 60, 246-250, 254-258
extrapolation of high to low dose rates, 44, 247
gamma rays, 61
genetic risk assessment, 92, 246
ICRP value, 246, 282, 293, 297
for mutagenesis, 246
rationale for, 247
for tumorigenesis, 77-79, 246-250
uncertainties in, 279, 284, 285, 286, 295, 296, 310
Dose effectiveness factor (DEF), 44, 246
Dose fractionation.
See also Diagnostic radiography
adaptive response, 78
and breast cancer risk, 26, 170, 176-177
and chromosome aberrations, 57
defined, 374
and dose-response relationship, 44, 55, 73, 74, 75-76
and hypersensitivity to radiation, 55
kinetics, 75-76
and leukemia risk, 73
and lung cancer risk, 176
and mutagenesis, 57
and mutation rates, 99
and tumorigenesis, 68, 73, 75-76, 78-79, 182
Dose rate
and chromosome aberrations, 24
defined, 374
and dose-response relationship, 73, 74
extrapolation from high to low dose, 50
and mutation rate, 100 n.1
in radiotherapy patients, 156-157
and RBE, 24
reduction factor, 100 n.1, 116, 130-131
Dose-rate effect
cell cycle phase and, 49-50, 55
defined, 374
life shortening, 77
protracted dose distinguished from, 77
Dose-rate effectiveness factor (DREF)
for solid tumors, 146
Dose-response relationships.
See also Radiosensitivity
adaptive response and, 45, 50-53, 62, 89
animal models, 73-75, 89, 245, 246, 249, 255, 256
atomic bomb survivors, 6, 24, 45, 68, 72, 137, 140, 142, 143, 144, 145-146, 147, 149, 150, 151, 152, 153, 245, 256
Bayesian statistical analysis of, 246-250, 254-258
benign neoplasms, 151
biophysical modeling, 45, 139, 246
breast cancer, 74, 76, 86, 149, 157-158, 159, 160, 163, 168, 170, 172, 176, 178-180
bystander effect and, 45, 53, 54-55
cancer mortality, 145
for cancer-risk assessment model, 245-246, 262, 269, 274
cell killing/lethality, 55-57, 75, 78
Chernobyl accident and, 224, 225, 226-227
in children, 10, 161, 162, 168, 169
chromosome aberrations, 24, 25, 45-46, 57-59, 60-61, 73, 74, 256, 257
chronic exposure, 43
control population, 43
DDREF and, 44-45, 60, 246-250, 254-258
DNA damage and response, 31, 73, 246-247
dose fractionation and, 44, 55, 73, 74, 75-76
environmental radiation exposures, 224-225, 233, 234, 235
in epidemiological studies, 132, 137, 139, 140, 189, 208, 245, 246
extrapolating from high dose to low dose, 44-45
genomic instability and, 45, 46, 48, 49, 60-61
hypersensitivity to radiation and, 55-57
for internally deposited radionuclides, 43, 276
LET of radiation and, 9, 24, 43, 45, 126, 158, 245
leukemia, 71, 72, 73-74, 76, 77, 142, 144, 157, 158, 160, 161, 163-164, 165, 183, 184, 245, 264, 295
life shortening, 76-77, 89, 249, 255, 257, 258
linear, 13, 47, 60, 62, 73, 74, 77, 137, 201, 246, 247, 250, 264, 269, 299
linear no-threshold, 246
linear-quadratic, 7, 24, 43-44, 47, 74, 201, 247-248, 250, 255, 257, 274, 280
at low doses, 10, 43-45, 57-62, 73
lung cancer, 74, 76, 158, 160, 163, 201, 255, 262
in lymphocyte assays, 57, 58, 60
maxiumum likelihood estimates, 250
modifying variables, 264-266
mouse studies at low doses, 58, 60, 73-75, 76, 78, 126
mutations, 47, 50, 57, 59-60, 61, 73, 108, 113, 114, 245, 246
occupational exposures, 189
quadratic, 74
radiotherapy-related cancers, 157-170
signal transduction pathways and, 62
single-tracks with repair factor, 44-45
solid tumors, 74-75, 142, 144, 145-146, 201, 245, 298
temporal relationships, 45, 50, 60, 61-62, 68, 70, 73-77, 245-246
thyroid cancer, 149, 160, 162, 167, 168, 169, 182, 215, 224, 225, 276
thyroid diseases, 153
translocations, 57, 58, 60, 61
in tumorigenesis, 12, 45, 50, 55, 59, 60, 61-62, 68, 73-77, 84, 89, 140, 245-246
in tumor-suppressor gene disorders, 84
uncertainties in, 246
Dosimeters, personal, 189, 193-194, 201
Dosimetry of ionizing radiation.
See also Microdosimetry
ankylosing spondylitis cohort, 164, 165
atomic bomb survivors, 6, 9, 10, 20, 24, 27, 72, 129, 134, 139, 141, 142-143, 144
and breast cancer, 159, 178-180
and cancer risk assessment, 241, 266, 268, 269
cervical cancer treatment cohort, 26, 157
Chernobyl accident, 114, 128, 129, 202, 203, 216-223, 224
defined, 374
diagnostic radiation, 155, 156, 170, 176
DS02 system, 27, 142, 269, 285, 296
fallout from nuclear weapons testing, 212, 213, 214
natural background radiation, 228
neutron component, 27, 143-144
nuclear-facility-related population exposures, 209-211, 212, 213, 214, 229-232
nuclear industry workers, 60, 138-139, 190, 191, 192, 193, 198-199, 201, 202, 203, 231, 233, 290
postpartum mastitis study, 163
radiotherapy recipients, 164, 165
uncertainties in, 3, 14, 128, 129, 139, 142, 169, 198-199, 233, 241, 266, 285
Doubling dose
advances in methodology, 94-101, 119, 122-124
atomic bomb survivor data, 7, 8, 118, 124, 130-131, 252
baseline frequencies of genetic diseases, 94-96, 115
BEAR Committee estimates, 96, 123
BEIR I estimates, 96, 97, 118, 122, 123
BEIR III estimates, 118, 122-124
BEIR V estimates, 12, 94-96, 100 n.1, 115, 118, 123, 124
children of atomic bomb survivors, 130-131
chromosomal diseases, 96
chronic multifactorial diseases, 12, 115, 119
dose rate and, 130-131
end points, 122, 123, 124, 130-131
estimation, 8, 93-94, 97-101, 113, 115
ESTR mutations, 126
extrapolation from mice to humans, 96-97, 109-111, 252
first-generation mortality and, 130
gametic, 130
Mendelian diseases, 12, 94-95, 115
minimum, 130
mouse vs human mutation rates, 12, 96-101, 113, 119, 122-124
multifactorial diseases, 95-96
mutation component, 8, 101-105, 113, 117
in nuclear test site populations, 128
radiation-induced mutation rates, 99, 101, 119
reciprocal, 93
spontaneous mutation rates, 8, 96-101, 119, 122, 123
uncertainties, 98-99, 130, 131
UNSCEAR estimates, 96, 122, 123, 124
Dpc4 gene, 69
Drosophila melanogaster, 53, 91
Duchenne’s muscular dystrophy, 93
Duodenal ulcer, 153
E
Edison, Thomas, 2
Effective dose
background radiation worldwide, 43
defined, 374
by source of radiation, 22-24
Electricité de France, 191, 192, 197
Electromagnetic radiations. See Gamma rays;
X- rays
Electrons
binding energy, 20
ionization of water, 20, 21, 29-30
penetration depth, 21
Endocrine glands, cancer of, 168
Endometrial carcinoma, 67, 80, 86
Energy transfer process
biological damage process, 20
direct effects, 26
indirect effects, 29-30
of low-LET radiation, 20-21
Environmental radiation exposures
from atmospheric releases, 212-215
cancer incidence and/or mortality, 209-212
cesium-137, 215
Chernobyl accident, 215-228, 234-235, 236
children, 208, 209-210, 211, 212, 213, 215-226, 229, 233, 234, 235-238
cohort studies, 212, 213-214, 229, 231-232, 235
congenital defects, 211, 229, 230, 232, 233, 235
dose-response relationships, 224-225, 233, 234, 235
ecologic studies, 208-211, 212, 215, 216-223, 228-229, 235, 236-237
fallout from weapons tests, 212-215, 234, 235
and leukemia, 209, 210, 211, 212, 214, 216-222, 226-227, 228-229, 230, 231, 232, 233, 235
limitations and weaknesses of studies, 207-208, 233, 235
and lymphoma, 209, 217, 228-229, 230, 231
natural background, 3, 4, 8, 31, 43, 209, 228, 236-237
nuclear facility proximity and, 208-212, 229, 230, 233, 234, 235-236
parental preconception, 211, 212, 215, 228-233, 235, 237
and reproductive outcomes, 211, 229, 231, 232, 233
surrogates for, 207
Three Mile Island accident, 208, 209, 211
and thyroid cancer, 215-226, 234, 236
uranium mines, 211
Epidemiological studies.
See also specific cohorts
analysis of data, 136-139
assessment of associations, 132-133, 139-140
BEIR V principal environmental studies, 208, 209-214
bias, 132, 133, 135-136, 139, 140, 152, 173, 187, 208
Bradford Hill criteria, 140
case control, 133, 134-135, 136, 148, 172, 190, 207, 208
cohort, 133, 134, 135, 136, 173, 207, 208
comparability in study design, 133, 135-136, 241
confounding, 133, 136, 138, 141, 199-201, 207, 240
design issues, 135-136, 187, 198, 207-208, 287
dose-response relationships, 132, 137, 139, 140, 189, 208, 245, 246
ecologic design, 10, 207, 208, 215, 216-223, 226
exposure assessment, 134-135, 137, 139, 193-194, 207
extrapolation of risks from, 240-241
high-dose studies, 139
hybrid (“nested”), 135, 148, 190
interpretation of data, 139-140, 141
of LET-related risks, 24-26
linear relative risk model, 137, 138-139
measures of association, 132, 137
nuclear industry workers, 189, 190-193
pooled analyses of data, 169, 180, 181, 243, 268-269
randomized intervention trials, 133-134
retinoblastoma, 84
statistical power, 136, 189, 204, 208, 241, 245
tools of statistical inference, 137-138
types, 133
uncertainty in, 133, 207, 208, 265
Epidermal growth factor receptor (EGFR), 55
Equivalent dose, defined, 374
Escherichia coli, 36
Esophageal cancer, 147, 148, 149, 164, 170, 215, 269, 282, 294
Ethylnitrosourea (ENU), 69
Etoposide, 130
age at exposure and, 149
European Childhood Leukemia-Lymphoma Incidence Study, 226
Excess absolute risk (EAR), 269, 270, 271, 272, 273, 274, 275, 276, 277
application, 137, 143, 240-241
breast cancer, 12, 25, 26, 149, 168, 243, 287
comparison of alternative models, 300
linear dose-response function, 299
parametric model, 306
model fitting, 296, 299, 304-306
site-specific cancer in atomic bomb survivors, 147, 149, 304-306
solid cancer mortality, 145
tumorigenic radiosensitivity, 84
uncertainty in, 285-286
Excess relative risk (ERR), 144, 268, 269, 271, 272, 273, 274, 275, 276, 277
age at exposure and, 148, 285-286, 296, 297-298, 299, 300, 301
bias and, 152
breast cancer, 12, 25, 26, 148, 149, 159, 164, 175, 240, 242, 243, 244
coherence of BEIR VII estimates with other estimates, 287-288
comparison of alternative models, 300
defined, 132, 137, 143 n.3, 374
follow-up period and, 297
in heritable retinoblastoma patients, 84
linear dose-response function, 299
lung cancer, 12, 148, 150, 159
excess relative risk, 132, 143, 285-286
for radioepidemiological tables, 306
RERF, 301
site-specific cancer in atomic bomb survivors, 147-150
site-specific cancers, 303-304
skin cancer, 148
solid cancer mortality, 145
statistical precision, 137-138
stomach cancer, 12, 287, 288, 289, 301-302
stratified baseline risks, 299
thyroid cancer, 12
uncertainty in, 285-286
Expanded simple tandem repeat (ESTR) loci, 113-114
Experimental studies
defined, 133
potential disease phenotypes, 112-113
RBE of neutrons, 28-29
spontaneous vs. induced mutations, 124-125
Exposure to ionizing radiation.
See also Dosimetry of ionizing radiation;
Environmental radiation exposures;
Low doses;
Occupational radiation exposure;
Protracted exposure
annual worldwide, from natural sources, 2, 3, 4
atomic bomb survivors, 6, 9, 129, 139, 141
chronic, 11, 43, 56, 68, 129, 280
CT scans, 4-5
defined, 374
factors affecting, 4
hypoxic conditions, 34
priming dose, 51-53, 55, 78, 251
scenarios, 4-6
surrogate indicators, 207, 208
uncertainties in data, 3, 139, 174
U.S. population, 3-4
Extrapolation of data
from animals to humans, 73, 96-98, 109-111, 114, 115, 252
BEIR V report, 115
cross-population, 85, 88, 240-245, 253-254, 265, 266, 275-276, 278-281, 284, 285, 286, 292
from high dose to low dose, 9, 29, 44, 50, 54, 62, 146, 247, 296
from in vitro to in vivo transformation systems, 52, 53
Moolgavkar and Knudson two-stage clonal expansion model, 241, 253-254
postirradiation cancer mechanisms and, 241
F
FA-A to FA-C genes, 80
Fabry’s disease, 93
Fallout. See Nuclear weapons testing
Familial adenomatus polyposis, 67, 80, 82, 83, 98
Familial hypercholesterolemia, 98, 125
Fanconi’s anemia, 80
Fbxw7 gene, 69
Fenton oxidants, 30
Fetal exposure to radiation
atomic bomb survivors, 151
and cancer in childhood, 6
IEER issues, 330
and mental retardation, 1
Fifteen-Country Workers Study, 336
Finite-locus threshold model, 105-108, 124
Fluorescence in situ hybridization (FISH) method of chromosome painting, 45-46, 57
Fluoroscopy
and breast cancer, 26, 170, 176, 177, 180, 243
Canadian epidemiological study, 176, 287
and lung cancer, 174, 175, 176, 288, 289
Massachusetts tuberculosis cohort, 170-171, 174, 176, 243, 273, 287, 292
and skin cancer, 2
14-3-3 proteins, 39
Free radicals, DNA damage from, 19, 29-30, 239
French Commissariat a l’Energie Atomique, 28, 190
G
GADD45 gene, 39
Gall bladder cancer, 147, 148, 149, 269
Gamma rays
bystander effects, 54-55
cancer risk estimates, 276
damage mechanisms, 26-27
DDREF, 61
defined, 374
dose-rate effect, 28
dosimetry for atomic bomb survivors, 6, 142
environmental exposures, 212
extrapolation to X-ray exposures, 24
high-energy, 24
mutations in mice from, 126
occupational exposures, 204
photon energies, 19, 20, 21, 22, 24, 276
RBE, 21, 22, 24, 25, 28, 126, 276
signal transduction study, 56
terrestrial, 30
Gastrointestinal cancers, 218
Gene amplification, 47, 49, 72
Gene-environment interactions, 12, 86, 87, 88
Genes.
See also specific genes
antibody, 34
autosomal recessive disorders, 80
basic concepts, 327
breast cancer, 67, 79, 80, 82, 83, 84, 85-86, 243
caretaker, 67
checkpoint kinase, 86
deletions, 11, 58, 61, 66, 67, 86, 109, 110, 111, 112, 119, 124, 125
DNA repair, 36, 37, 39, 40, 42, 71, 86, 87-88
epigenetic silencing events, 66, 67
functional polymorphisms, 12, 86-88, 113, 114
haploinsufficiency, 125
human counterparts in mice, 98-99
interactions (epistasis), 12, 70, 108
low-penetrance, 85-88
oxidative damage resistance, 40-42
proto-oncogenes, 81-82
radiation resistance, 30, 40-42
radiation-responsive, 39
recoverability of induced mutations in live births, 109-111, 124, 125
tumor-supressor, 39, 65, 66, 69, 80, 80, 81
Genetic diseases.
See also Genetic susceptibility to cancer;
specific diseases
absolute risk, 110
autosomal dominant, 79, 80, 81, 92, 94, 95, 96, 97-98, 101, 102, 103-105, 110, 112, 115, 116, 117, 125
autosomal recessive, 79, 80, 81, 92-93, 94-95, 96, 101, 104, 105, 110-111, 115, 117-118
baseline frequencies, 12, 92, 94-95, 96, 115, 117-118
basic concepts, 328
congenital, 93, 95, 105-106, 112, 115, 117, 119
defined, 92
experimental data, 112-113
frequency, 105
inborn errors of metabolisms, 113
marker, 125
Mendelian, 92-93, 94-95, 96, 98, 105, 111, 112, 113, 115, 119
MIM maps, 125
minisatellite polymorphisms and, 113, 114
multifactorial, 8, 93, 95, 96, 101, 112, 115, 117, 119
multisystem developmental abnormalities, 12, 112
mutation component, 98, 101-105, 117
potential phenotypes, 111-113
PRCF estimates, 110-111
“radiation-inducible,” 92
risk estimation by class of, 94, 115, 116
spontaneous mutation rates, 97-98, 109
sporadic cases, 108
X-linked, 92, 93, 94, 95, 96, 97, 98, 101, 104-105, 110, 115, 116, 125
Genetic effects of radiation.
See also Chromosome aberrations;
DNA damage;
Mutations
animal studies, 12, 68-70, 73, 82-83, 92
background data from humans, 8
basic concepts, 328
BEIR I estimates, 94
cardiovascular disease, 95, 96
in children, 8-9, 68, 114, 118, 161
detection, 8
disease liability concept, 107, 120-121
germ-cell mutations at ESTR loci and, 113-114, 125-130
heritability concept, 121-122
at human minisatellite loci, 126, 128-130
models of multifactorial diseases, 120-122, 252
multifactorial threshold model, 120-121, 252
Genetic risk assessment.
See also Mutation component of genetic diseases
advances since BEIR V, 115-116
in atomic bomb survivors, 8-9, 91, 92, 114, 115, 118, 131, 252
autosomal dominant disorders, 94, 111, 115, 116, 117
autosomal recessive diseases, 94, 112, 115
baseline disease frequencies, 12, 94-96, 115, 117, 252
BEIR III estimates, 94-95
BEIR V estimates, 12, 94-95, 96, 115-116, 117-118, 252
chromosomal diseases, 115, 117
chronic multifactorial diseases, 115, 116, 117
congenital abnormalities, 115, 116, 117, 120
current estimates, 116, 118-120
doubling dose method, 8, 12, 93-101, 102, 111, 115, 117, 118, 119, 252
extrapolation of animal data to humans, 96-97, 109-111, 114
first postradiation generation, 94, 116, 117, 118
framework, 92
germ cell stages and, 92
goal, 92
mouse data, 92, 96-97, 98-101, 109-111, 112-113, 114, 115-116, 252
mutation component, 12, 81, 94, 101-113, 115, 116, 117, 119, 252
overlap in estimates, 119-120
potential recoverability correction factor, 12, 109-110, 115, 119, 252
reconciliation of present and past estimates, 117, 118
reproductive outcomes, 252
second-generation progeny, 116
spontaneous mutations, 8, 96-101
UNSCEAR estimates, 92, 94, 95, 96, 109, 111, 112, 115, 118
X-linked disorders, 94, 111, 115, 116, 117
Genetic susceptibility to cancer.
See also Radiosensitivity;
Tumorigenesis, radiation induced
age of onset in carriers, 81
autosomal recessive disorders, 79, 80, 85
breast cancer, 67, 79, 80, 82, 83, 84, 85-86, 87-88, 103, 243
and cancer risk assessment, 85-87, 88, 241, 251
cancer-prone human disorders, 79-81, 85
cellular mechanisms, 79, 81-82
children, 161
colonic and other neoplasms, 66, 67, 79, 80, 86-87
DNA repair defects and, 71, 79-81, 87
genes of low penetrance and, 85-88
heritable radiosensitivity and, 82-85
human data on, 83-87
leukemia, 80
low-penetrance genes, 85-89
lymphoma, 80
proto-oncogenes and, 79, 80, 81-82
risk modeling, 81-82, 85, 86, 88, 120-122, 251
secondary cancer in radiotherapy patients, 161
species variation in, 73
spontaneously arising human tumors, 66-67
strengths and weaknesses of current estimates, 118-120
thyroid cancer, 80, 81-82, 244, 246
tumor suppressor genes and, 79, 80, 81
twin studies, 88
to virally associated neoplasia, 79
X-linked disorders, 79
Genomic instability, radiation-induced, 11, 43
apoptosis and, 48-49
in bone marrow cells, 72
and cancer risk assessment, 251
in CHO cells, 58
chromatid instability, 70-73
chromosomal aberrations and, 46, 47-48, 54, 58, 59, 60-61, 70, 251
defined, 47
delayed, in somatic cells, 127
DNA repair defects and, 48, 49, 72
dose-response relationship, 45, 46, 48, 49, 60-61
gene mutations and, 61, 66, 68, 70, 87, 88, 113, 126-127
guardian-of-the-genome hypothesis, 48-49
in hematopoietic cells, 70-71
hypersensitivity to radiation and, 57, 71
manifestations, 47, 54, 55, 57, 58, 70
at minisatellite and ESTR loci, 113, 126-127
modeling, 251
in mouse mammary epithelial cells, 71-73
in mouse melanocytes, 58
persistent, 46
reactive oxygen species and, 48
RBE, 71
target and lesions resulting in, 48
telomere-associated, 48, 71-73, 251
transgenerational, 127
and tumorigenesis, 39, 46, 48-49, 65, 67, 69, 70-73, 78, 251
in zygotes, 127
Genotype, and adaptive response, 53
Germ cells.
See also Genetic diseases;
Genetic susceptibility to cancer
defined, 374
minisatellite loci, 113-114, 128-129
mutations, 6, 8, 81, 97, 109, 113-114, 125-130
polymorphisms, 87
stages and radiation conditions of relevance, 92
German Childhood Cancer Registry, 226
Growth and development effects
animal studies, 115
DNA repair defects, 34
human studies, 8
mental deficiency, 112
multisystem abnormalities, 112, 115
Guardian-of-the-genome hypothesis, 48-49
H
H2AX histone protein, 31, 36, 50
Hamsters
Chinese hamster ovary (CHO) cells, 48, 55, 58, 59, 61
DNA repair rates in Chinese hamster V79 cells, 52
malignant transformation in embryo cells, 59, 61
mutation studies, 59
Hanford Site, 135, 190, 191, 192, 193, 197, 199, 200, 213, 215, 230, 234, 235, 276
HAP1, 32
Hardy-Weinberg equilibrium, 102
Health end point data, 76-77, 142
Heart disease. See Cardiovascular disease
Heat shock-related proteins, 52-53
Heavy metal exposures, 128, 242
Helicobacter pylori infection, 241-242, 302
Hemangiosarcomas, 150
Hematopoietic cells, chromatid instability in, 70-71
Hemochromatosis, 93
Hepatoblastoma, 150
Hepatocellular carcinomas, 150, 242
Heritable genetic effects in humans. See Genetic diseases;
Genetic effects of radiation;
Genetic risk assessment;
Genetic susceptibility to cancer
High-LET radiation.
See also Alpha particles;
Neutrons
bystander effects, 53-54
carcinogenesis, 49
chromosome aberrations, 45
damage mechanisms, 2, 19, 36, 45
defined, 375
dose-rate effects, xi
epidemiological studies, 198-199
physics and dosimetry, 19, 198-199
sources, 4
Hiroshima Tumor Registry, 268
hMre11/hRad50/Nbs1 DNA-binding and exonuclease complex, 35, 36, 39
Hodgkin’s disease, 12, 130, 151, 158-159, 174, 175, 176, 177, 242-243
Hormesis, 11
adaptive response, 333
animal studies, 334
cell studies, 333
and epidemiology, 334-335
life span data, 334
theoretical considerations, 332
tumor incidence data, 334
Hormones
and breast cancer, 76, 157-158, 159, 168, 169, 241, 243
and thyroid cancer, 244
and tumorigenesis, 75
HPRT gene, 44-45, 47, 51, 53, 54, 58, 61
hRad54 protein, 35
HRAS1 gene, 113
HSP70 proteins, 52-53
HSP90 proteins, 52
HTLV-1, 244
Human cell lines/systems
chromosomal instability in diploid fibroblasts, 72
fibroblasts, 51, 54, 55, 57, 58, 72
Hela hybrid system, 52, 59, 62
hypersensitivity to killing, 56
keratinocytes, 54-55
malignant transformation, 59, 62
MCF-7:W58 breast cancer, 56
mutagenesis in lymphoblastoid cells, 51, 59-60
myeloid tumor, 56
oocyte radiosensitivity, 99
TK6 lymphoblasts, 58, 59-60, 61
Human studies.
See also Epidemiological studies
bone cancer, 84
genomic instability, 71
mutations at minisatellite loci, 113, 114, 128-130
Hungarian congenital disease population, 95
Hydrogen peroxide, 29, 30, 31, 40, 41, 42, 50, 53
8-Hydroxyguanine, 31
Hydroxyl radical
bystander effect and, 54
damage mechanisms, 29-30
production during energy transfer processes, 31
Hypersensitivity to radiation at low doses, 11, 32, 45, 47, 51, 55-57, 71, 82, 239
Hypertension, 93, 95, 111, 153
Hyperthyroidism, 165-166, 169, 182, 185, 226, 234
Hypothyroidism, 226
Hypoxanthine-guanine phosphoribosyl transferase (HGPT) mutation, 44-45
I
IDDM2 gene, 113
Immune disorders, virally associated neoplasia, 79
Immune response, 66-67
Immunologic rearrangement, 35
Immunophilins, 52
In vitro assays. See also;
Human cell lines/systems;
Lymphocytes;
individual animal species
adaptive response in mammalian cells, 51, 52, 62
bystander effect in, 53, 54-55
chromatid instability in bone marrow cells, 71
chromosome aberrations in human cells, 24, 53, 58, 61, 72
defined, 375
extrapolation to in vivo transformation systems, 52, 57
genomic instability, 58
of LET-related risks, 24
M5S mouse embryonic skin cells, 52
malignant transformation, 51-52, 61-62
priming dose, 52
RBE, 24
somatic mutagenesis, 69
trypsinization and replating, 52, 62
Inelastic scattering, 20
Infertility, hormonal, 164
Institut Gustave Roussy, 160, 161, 169
Institute for Energy and Environmental Research, issues raised by, 330-331
Institute of Haematology and Blood Transfusology (Belarus), 203
Internally deposited radionuclides.
See also Iodine-131;
other specific radionuclides
alpha particles, 199-200
cancer risk estimates, 200, 276
Chernobyl accident and, 276
dose-response relationships, 43, 276
and lung cancer, 200
measurement problems, 199-200
nuclear industry worker exposure, 190, 199-200
and prostate cancer, 200
International Agency for Research on Cancer, 336
International Cervical Cancer Survivor Study, 181
International Childhood Cancer Survivor Study, 181
International Classification of Diseases, 95
International Commission on Radiation Units and Measurements, 22, 375
International Commission on Radiological Protection, 22, 81, 85, 103, 105, 109, 124, 165, 197, 246, 274, 282, 283, 292-293, 294, 297, 375
Intestinal carcinoma, 69, 70, 87, 88, 166
Iodine deficiency, 244
Iodine-131
adaptive response to, 51
childhood exposure, 68, 169, 173, 215
diagnostic exposures, 171, 173, 234
dose-response relationship, 235, 276
environmental exposures, 68, 209, 214, 215, 233-235
radiotherapy-related risks, 161, 165-166, 171, 182, 234
and salivary gland tumors, 165
thyroid cancer, 68, 161, 165, 171, 182, 214, 215-226, 233-235, 276
Iododeoxyuridine (125Idu), 48
Ionizing radiation.
See also Alpha particles;
Beta particles;
Exposure to ionizing radiation;
Gamma rays;
High-LET radiation;
Low-LET radiation;
Natural background radiation;
Neutrons;
X-rays
background, 30-31
chemical aspects, 29-32
damage mechanisms, 6, 26-27, 29-30, 40-42, 239
detection, 2
discovery, 1-2
late effects, 11
low doses defined, 2
photon spectral distributions, 20-22
physical aspects, 19-29
track structure, 21, 26-27, 29, 55, 62
see also Gamma rays;
X rays
U.S. population exposure, 3-4
Iron-59, 200
I-SceI endonuclease, 48
Ischemic heart disease, 95, 153
Israel Tinea Capitis Study, 68, 155, 156, 166-167, 181, 182, 183, 273, 292
J
Japanese nuclear workers, 198
Jaslovske power plant, 197
Juvenile osteocondrosis, 95
K
Kidney carcinoma, 66, 149, 161, 164, 166, 227, 228, 269, 282, 293, 294
L
Laboratory animals. See Animal studies;
specific animals
Late Effects Study Group, 161, 162
Latent health effects
RBE of neutron doses and, 27
Lead, 200
LET. See Linear energy transfer
Leukemia
acute lymphatic, 144, 210, 218, 226
acute myelogenous, 68-69, 144, 153, 164, 227
age factors and, 144, 264, 288
alpha particles and, 71
analysis of human data, 296, 307-308
animal studies, 68-70, 71, 72, 73-74, 87
in ankylosing spondylitis cohort, 164, 165, 183, 289
in atomic bomb survivors, 68, 72, 142, 143, 144, 153, 172, 244, 245, 269, 307-308
BEIR V model, 246, 282, 283, 292
breast cancer survivors, 159-160
caretaker gene, 67
in cervical cancer survivors, 157, 158, 183, 289
chemotherapy-related, 86, 160, 244
Chernobyl accident and, 203-204, 216-222, 225-227
children, 84, 161, 168, 172, 209, 210, 211, 212, 214, 216-222, 226-227, 233, 244
chromosome aberrations and, 65, 68-69, 72, 74
chronic lymphocytic, 157, 159-160, 162, 212, 244, 283, 307
coherence of BEIR VII estimates with other studies, 288, 289, 294
deaths, 144
diagnostic irradiation and, 170, 171, 172
dose fractionation and, 73
dose-response relationship, 71, 72, 73-74, 76, 77, 142, 144, 157, 158, 160, 161, 163-164, 165, 183, 184, 245, 264, 295
environmental exposures and, 209, 210, 211, 212, 214, 216-222, 226-227, 228-229, 233, 244
EPA model, 282
etiology, 243
excess relative risk, 12, 295, 307-309
frequencies, 77
genetic susceptibility, 80, 86, 87
human data, 72
ICRP model, 282
in utero exposures and, 172
initiation mechanisms, 66-67, 68, 74
internally deposited radionuclides and, 200
lymphocytic (nonacute), 67, 164
medical-exposure-related risks, 12, 289-290
misclassification of cause of death, 153
models, 144, 246, 264, 273-274, 307-308
monocytic, 171
in nuclear industry workers, 14, 190, 191, 196, 197, 198, 199, 200, 201, 202-204, 275, 288
nuclear weapons testing and, 214
quantitative studies, 73-74
in radiologists and radiologic technologists, 189, 204, 205
radiosensitivity of bone marrow, 173
in radiotherapy recipients, 84, 157, 158, 160-161, 162, 163-164, 165, 166, 168, 183-185
registry data, 142
risk assessment, 143, 144, 245, 246, 273-274, 285, 295, 296, 307-308
risk estimates, 173, 183-185, 277, 278, 280-282, 284, 289-290, 294, 307-308
risk factors, 244
in tinea capitis cohort, 166, 183
temporal distribution, 144
uncertainties in risk, 284, 285
X-rays and, 71
Life shortening studies
in atomic bomb survivors, 153-154
and DDREF, 246
dose-response relationship, 76-77, 89, 153, 249, 255, 257, 258
as proxy for mortality, 28-29
wasted radiation concept, 77
Life span, and paternal effect for mutations, 97
Life Span Study, 9, 12-13, 26, 141-154, 246-250, 267-268, 285-308, 375.
See also Atomic bomb survivors
Li-Fraumeni syndrome, 79, 80, 81, 82, 83, 84
Linde facility, 190
Linear energy transfer (LET).
See also High-LET radiation;
Low-LET radiation;
Restricted LET
and chromosome aberrations, 45
consistency with other studies, 57
and DNA damage, 20, 26-27, 31, 245
and dose-response relationship, 9, 24, 43
in vitro studies, 24
microdosimetric analogue, 22, 23
protons and electrons in water, 20
as quality-of-radiation measure, 22-24
radioepidemiologic studies, 24-26
RBE variation with, 21
track average, 19 n.1
Linear no-threshold (LNT) model, 9-10
basic assumption, 7
DDREF adjustment, 7
defined, 375
description, 6-8
dose-response relationship, 246
lifetime-risk example, 7-8
Linear relative risk model, 137
applications, 138
equation, 138
statistical inferences, 138-139
Linear-quadratic model, 6
DDREF estimates, 246
defined, 375
dose-response relationship, 7, 24, 43-44, 47, 74, 201, 247-248, 250, 255, 257, 274, 280
for leukemia, 14, 246, 292, 295
Lineoleic acid 13-hydroperoxide, 40
Liver cancer
age at exposure and, 150
alpha particles and, 68
atomic bomb survivors, 147, 148, 149, 150, 269, 298
baseline lifetime risk estimates, 278
death certificate data, 150
diagnostic irradiation and, 68
dose-response relationship, 150, 201
etiology, 242
excess relative risk, 148, 301, 302
hepatitis antigen status and, 150, 242
human studies, 68
metastatic, 150
multiplicative model, 242
risk models and estimates, 242, 272, 278, 279, 280, 282, 284, 285, 294, 301, 303-306
Thorotrast exposure and, 150
Liver disease and cirrhosis, 153, 242
Los Alamos National Laboratory, 192, 197
Low doses
breast cancer risk, 86
DNA damage, 31
dose-response relationships, 10, 43-45, 57-62, 73
hyper-radiation sensitivity at, 55-57
neutron RBE at, 28-29
potential for beneficial effects, 10
probability of cell damage, 9-10
protracted exposure, 31
solid tumors, 74
Low-LET radiation.
See also Gamma rays;
X-rays
annual worldwide exposure from natural sources, 2, 3, 4
bystander effects for, 54-55
carcinogenic effects, 245
cell lethality, 55-57
damage mechanisms, 26-27
defined, 375
dose units, xi
dose-response relationships, 45, 126, 158, 245
epidemiological studies, 199
mutation rates, 9
physics and dosimetry, 19, 21, 199
RBE variation with dose rate, 21, 24
track structure, 21, 43-44, 55
Lung cancer.
See also Respiratory system cancer
additive risk model, 150, 159, 242, 276
age and, 147
alpha particle exposure and, 242
animal studies, 28, 50, 74, 76, 87
in ankylosing spondylitis cohort, 164, 174
in atomic bomb survivors, 68, 147, 148, 150, 242, 262, 269, 276
baseline lifetime risk estimates, 278
in benign breast disease cohort, 174
in breast cancer survivors, 160, 174, 175
in cervical cancer survivors, 157
chemotherapy and, 159
childhood exposures and, 168, 175
diagnostic irradiation and, 170, 174, 176
dose fractionation and, 176
dose-response relationship, 74, 76, 158, 160, 163, 201, 255, 262
etiology, 242-243
excess relative risk, 12, 148, 150, 159
fluoroscopy and, 174, 175, 176, 288, 289
genetic susceptibility, 86-87
in Hodgkin’s disease cohort, 158, 159, 174, 176, 242-243
incidence, 174, 175, 242, 262, 278, 279, 284, 298, 303, 305
internally deposited radionuclides and, 200
latent, 159
medical-exposure-related risks, 174-176, 288
mortality, 174, 175, 242, 278, 280, 282, 298, 304, 306
multiplicative effects, 158, 159, 176, 242
in nuclear industry workers, 135, 190, 198
in peptic ulcer cohort, 163, 174, 175, 288
in radiologists and radiologic technologists, 204, 205
in radiotherapy-related risks, 157, 158-159, 160, 162, 163, 164, 166, 168, 174, 242, 288
repair kinetics, 76
risk models and assessment, 147, 148, 173, 174-176, 242, 244-245, 272, 275, 278, 279, 280, 282, 284, 288, 294, 303-306
sex differences, 150, 176, 284
in skin hemangioma cohorts, 174, 175, 176
smoking and, 87, 135, 138, 150, 158, 159, 174, 176, 198, 242, 276
uncertainties in risk assessments, 138
in uranium/underground miners, 138, 242
bystander effect, 53
chromosome aberrations, 45, 46, 51, 53, 57, 58, 59, 61, 86
dose-response relationship at low doses, 57, 58, 60
HPRT mutations, 60
Lymphohematopoietic tumors, 67, 71
Lymphoma
animal studies, 68, 73, 74, 76, 78
in atomic bomb survivors, 151, 153
in cervical cancer survivors, 157
Chernobyl accident and, 217, 227
chromosome aberrations and, 65
diagnostic irradiation and, 171
dose-response relationship, 73, 74, 77, 78, 151
environmental exposures and, 209, 217, 228-229
etiology, 78
frequencies, 77
genetic susceptibility, 80, 87
iodine-131 exposures, 171
misclassification of cause of death, 153
initiation mechanisms, 66-67, 68, 69, 70, 73, 74
and intestinal neoplasia, 88
mortality, 151
pathogenesis, 74
in radiologists and radiologic technologists, 204, 205
radiotherapy and, 164
target cells, 74
thymic, 12, 68, 73, 74, 76, 78
M
Macrophage oxidative bursts, 29
Mallinckrodt facility, 200
Malondialdehyde, 34
Mammary cancer.
See also Breast cancer, female
bystander effects, 55
chromatid instability and, 71-73
hormones and, 28
in rats, 28
Mammography, 4, 20, 21, 22, 24
Man-made radiation
sources, 3-4
U.S. population exposure, 3-4
MAPK, 39
Massachusetts General Hospital, 165
Mastitis patients, radiotherapy-related cancer, 26, 163, 177, 180, 243, 287, 292, 293
Mathematical models. See Models/modeling
Mayak plutonium production complex, 57, 190, 201-202, 212, 213, 214, 215, 235, 275, 276
Mayo Clinic, 165
Maximum likelihood principle, 138, 139
MCF-7:W58 cell lines, 56
Medical uses of radiation.
See also Diagnostic radiation;
Radiotherapy studies
adaptive response to, 51
age at exposure, 297
atomic bomb survivor data combined with, 146-147
and breast cancer, 12, 26, 84, 86, 157, 160, 163, 176-180, 287
cancer risk estimates, 12, 26, 173-187, 240, 241, 276, 286-290
and circulatory diseases, 12, 185-187
coherence of BEIR VII model with other studies, 286-290
epidemiological studies of exposure, 155-156
exposure limits, 43
and leukemia, 12, 183-185, 289-290
and lung cancer, 12, 174-176, 242
noncancer disease risk, 8, 12, 159, 160, 163, 185-187
occupational exposures, 204-205
physician population as surrogate for dose, 329
and RBE, 276
risk modeling, 138, 146-147, 276
and stomach cancer, 185
and thyroid cancer, 180-182, 287
Melanoma, 67, 80, 151, 161, 162, 190
Menadione, 40
Mendelian diseases, 92-93, 94-95
Mental retardation, 1
Mercury, 200
Metropathia hemorrhagica, 164
Michael Reese Hospital, 169, 181, 182
Microarray expression studies, 39, 53
Microdeletion syndromes, 112
Microencephaly, 80
Minisatellite loci, 113-114, 128-130
Mitochondrial electron transport, 49
Mitogen-activated protein kinase (MAPK), 55
MLH2 gene, 80
Model fitting
EPICURE software, 138, 143, 269, 296
to epidemiological data, 138, 269
leukemia data, 144
maximum likelihood estimates, 138, 139, 296
preferred risk models, 296-308
for site-specific cancers, 303-307
for solid cancers, 298-302
summing solid cancers, 279-280, 296
Wald method, 138
Models/modeling.
See also Cancer risk assessment;
Genetic risk assessment;
Uncertainties
absolute risk, 242, 244, 245, 253-254
adaptive response, 250-251
additive risk, 148, 150, 159, 240, 241, 242, 244-245, 254
age-at-exposure effects, 143, 264, 297-298
applications of, 264-265
Armitage-Doll, 262
atomic bomb survivor data, 143-144, 262, 263, 296-308
BEIR III, 138
BEIR V, 246
biologically based, 147, 262-263
bystander effects, 251
data quality and completeness, 265
defined, 375
dose measurement and, 139, 266
dose-response relationship, 45, 73-75, 89, 139, 245, 246, 249, 255, 256, 264-266
empirically based, 263-264
evolutionary population genetic, 105, 106
excess absolute risk, 143, 285-286
excess relative risk, 132, 143, 285-286
extrapolation from high dose to low dose, 9, 29
extrapolation from one population to another, 88, 240-245, 253-254, 266
finite-locus threshold, 105-108, 124
general mutagen model, 262
genetic susceptibility to cancer, 81-82, 85, 86, 88, 120-122, 251
genomic instability, 251
heritable effects of radiation, 92, 120-122, 251
Interactive RadioEpidemiological Program, 295
leukemia risk, 144, 246, 273-274
linear no-threshold, 6-10, 375
linear relative risk, 137, 138-139
medical-use-related risks, 138, 146-147
Moolgavkar-Knudson two-stage clonal expansion model, 241, 253-254, 262
multifactorial threshold model of disease liability, 93, 105, 107, 120-121, 252
multiplicative, 148, 163, 240, 241, 242, 243, 254, 297
NCRP review of, 293
parameter estimation, 264, 285-286
polygenic computational, 86
postirradiation cancer mechanisms and choice of, 241
preferred (BEIR VII) model, 6-8, 138, 244, 264, 269-278, 310-312
projections of cancer risk over time, 239-240
relative risk, 25, 26, 137, 138-139, 148, 149, 159, 164, 175, 240, 242, 243, 244, 253
solid cancers (all), 143, 269-271
threshold, 12, 74-75, 105-108, 120-121, 124
thyroid cancer, 273
Moolgavkar-Knudson two-stage clonal expansion model, 241, 253-254, 262
Mortality
ankylosing spondylitis cohort, 164, 165
atomic bomb survivors, 130, 131, 141, 142, 143, 144, 145, 147, 151, 152-153, 298-307
cancer, 2, 4-5, 28-29, 68, 76-77, 142, 144, 145, 151, 165, 170, 172, 174, 175, 176, 177, 181, 189, 191, 194-198, 200, 201, 202, 203, 204, 205, 209-212, 242, 243, 298-307
dose-response relationships, 145
healthy worker effect, 136
life shortening as proxy for, 28-29
lymphoma, 151
nonneoplastic disease in atomic bomb survivors scans, 141, 152-153
premature, 8
Mouse/murine studies
adaptive response, 51, 52, 53, 55, 78
AKR strain, 78
Apc-deficient genotype, 69, 70, 87
Atm-deficient, 82-83
BRCA-deficient, 82-83
cataracts, 115
C3H 10T1/2 cells, 50, 52, 55, 59, 61-62
C3H/HeN strain, 126
CBA strains, 71, 73-74, 78, 127
chemotherapy studies, 130
chromatid instability, 71-73
chromosome aberrations, 48, 57, 58, 119
congenital abnormalities, 115, 116, 131
dose-rate reduction factor, 100 n.1
dose-response relationships at low doses, 58, 60, 73-75, 76, 78, 126
doubling dose, 96-97, 98-101, 113
ESTR mutations, 113, 114, 125-127
extrapolation of data to humans, 73, 96-98, 114, 115
gene deletions in melanocytes, 58, 61
genetic effects of radiation, 92, 98-101, 109-111, 112-113, 115-116, 119
genetic models of tumorigenesis, 58, 61, 68-70, 82-83, 87
genomic instability as gene deletions, 58, 61
Harderian gland tumors, 74
human counterparts of genes, 98, 99
induced mutation rates, 92, 98-101
intestinal tract cancers, 87
lung cancer, 28, 50, 74, 76, 87
lymphoid neoplasms, 68-70, 73-74, 78
malignant transformation, 59, 61-62
mammary tumors, 50, 71-73, 74, 88
minisatellites, 125-126
ms5S embryonic skin cells, 51, 52
multisystem developmental abnormalities, 112-113
mutation studies, 8, 44-45, 47, 50, 56-57, 58, 60, 92, 98-101, 109-111, 112-113, 126-127, 130
oocyte killing, 24, 75, 98-99, 130
ovarian tumors, 50, 74, 75, 76
quantitative studies, 73-75
skeletal abnormalities, 115
solid tumors, 74-75
spermatogonia mutations, 50, 98
telomere-deficient strains, 48
Trp53-deficient, 78
tumorigenesis, 68-70, 71-75, 82-83
MRE11, 37
Mre11/Rad50/Nbs1, 38
MSH2 gene, 67
Mucoepidermoid carcinoma, 150
Multifactorial diseases, 8
baseline frequencies, 95-96
BEIR V estimates, 95, 96, 115, 117
BEIR VII estimates, 96
cancer as, 81
chronic, 95, 96, 105-113, 115, 117, 119, 124
congenital, 93, 95, 96, 112, 117
defined, 93
doubling dose, 94, 95-96, 101, 115
examples, 93
familial aggregation studies, 122
models, 93, 95, 105-106, 120-122, 124
multisystem developmental abnormalities, 112-113
mutation component, 81, 94, 101, 105-113, 117, 119, 124
potential recoverability correction factor, 119
prevalence, 95
threshold model, 93, 94, 120-121, 124
Multifactorial threshold model of disease liability, 93, 105, 107, 120-121
Multiple dystrophy, 98
Multiple endocrine neoplasia, 80
Multiple myeloma, 151, 164, 171, 204, 205, 214
Multiplicative effects, 148, 150, 163, 240, 241, 242, 243, 254, 297, 376
Mutagenesis
adaptive response, 51
apoptosis and, 49
bystander effects, 54
cell cycle phase and 49, 50, 81, 113
in cells hemizygous for autosomal APRT, 46
chromosome aberrations and, 47
DDREF, 246
DNA damage and repair processes and, 47, 65, 246
dose fractionation and, 57
dose-rate effects, 50
dose-response relationship, 47, 50, 57, 59-60, 61, 113
at ESTR loci in mice, 113-114
genetic context, 46
at HPRT gene, 47, 51, 53, 58, 59-60, 61
hypersensitivity to radiation and, 56-57
at minisatellite loci in humans, 113-114
radiation quality and, 47
RBE variation with LET, 24, 47
in somatic cells, 46-47, 113, 246
in spermatogonia, 60
target genes, 47
in TK6 human lymphoblastoid cells, 59-60, 61
Mutation component of genetic diseases
application, 102
autosomal dominant diseases, 102, 103-105, 111, 115, 116, 119
autosomal recessive diseases, 104, 105, 110-111, 115
BEIR V estimates, 94, 106, 115
chronic multifactorial disease, 105-113, 119
concept, 94
congenital abnormalities, 105-106, 111, 116
dose-response relationship, 108, 245
for early postradiation generations, 106, 116
estimation, 103-113
finite-locus threshold model, 105-107, 108, 111, 124
first-generation increase in mutation rate and, 103, 104, 105, 106-108, 109, 119
gene-gene interactions (epistasis) and, 108
Hardy-Weinberg equilibrium, 102
heritability of liability concept, 105, 106, 107, 111, 121-122, 124
multisystem developmental abnormalities, 112
murine studies of induced mutations, 109-111, 112-113, 116, 124-125
mutation-selection balance, 94, 102, 103, 105, 106, 107, 109, 117
nonsporadic cases, 103
numerical estimates, 104-105
permanent increase in mutation rate and, 104, 105, 106-109
“phenotypes” of human diseases, 111-113
population genetic concepts, 102
potential recoverability correction factor, 109-110, 111, 125
rationale for, 101-102
spontaneous mutations in humans, 109-111, 124-125
strengths and weaknesses of, 119
UNSCEAR, 109
X-linked diseases, 104, 105, 111, 115, 116, 119
Mutation rates
age and, 97
animal studies extrapolated to humans, 96-98
in atomic bomb survivors, 6, 114, 129, 130-131
calculating rates in mice, 99-100, 119
in children of atomic bomb survivors, 114
in children of Chernobyl inhabitants/cleanup workers, 114, 128, 129-130
dose fractionation and, 99
in early postradiation generations, 106
effects at equilibrium following permanent increase, 106-109
at ESTRs, 126-127
family size and, 97
in first generation, 105, 106, 108, 129
and fitness of a population, 102
and genetic disease risk in humans, 109-111
in human genes, 97-98
mice, 92, 96-101, 109-111, 114, 126
at minisatellite loci, 114, 128-130
parental birth year and, 129
sex differences, 96-97, 119, 128
spermatogonial stage, 100, 113
spontaneous, 97-101
X-linked diseases, 98
Mutations.
See also Chromosome aberrations;
DNA damage;
Genetic effects of radiation;
Spontaneous mutations
in atomic bomb survivors, 6
autosomal dominant, 98
basic concepts, 327-328
biochemical (null enzyme), 98, 99, 131
broad-sense and narrow-sense heritability and, 121-122
and cell death, 47
Chernobyl accident and, 128-129
complex, 51
congenital abnormalities, 131
defined, 327
deletions, 36, 40, 47, 54, 65, 109
dominant negative, 125
dose-response relationship, 47, 57, 59-60, 73, 113, 114, 246
in Drosophila melanogaster, 8
electrophoretic, 131
first generation, 130-131
see also Genetic susceptibility to cancer
human minisatellite loci, 128-129
human tumors, 66-67
indirect, 127
intragenic, 109
lethal, 47
loss-of-function, 66, 67, 81, 125
low-penetrance, 85-88
at minisatellite loci in humans, 113, 114, 128-129
missense or nonsense, 125
mouse studies, 8, 44-45, 47, 50, 56-57, 58, 60, 92, 98-101, 109-111, 112-113, 125-126
multilocus, 46
multisite DNA fingerprinting, 129
potentially recoverable, 109-111, 112
radiation-induced tumors, 67-68, 239
recoverability of genes in live births, 109-111, 124, 125
relative risk, 6
reversion, 47
single-gene, 46
spontaneously arising tumors, 66-67, 239
trinucleotide repeat expansions, 125
Tradescantia, 24
and tumor susceptibility, 66-67, 242
Myelodysplastic syndrome, 153
MYH gene, 67
Myocardial infarction, 153
Myotonic dystrophy, 92
N
Nagasaki Tumor Registry, 268
National Council on Radiation Protection and Measurements, 43, 293, 376
National Institutes of Health
cancer risk model, 138, 268, 269, 273, 277-278, 293
radioepidemiological tables, 294-296, 299
National Radiological Protection Board, 82, 85, 293
National Registry of Radiation Workers (UK), 14, 190, 193, 195, 196, 197, 198, 200, 230, 290
National Research Council
Committee on Atomic Casualties, 91
Committee on the Biological Effects of Atomic Radiation, 91
Committee on the Biological Effects of Radiation, 91;
see also BEIR entries
Natural background radiation
annual effective dose per person worldwide, 2, 3, 4, 30, 43
chemical aspects, 30-31
defined, 373
DNA damage, 30-31
dosimetry, 228
ecologic studies, 228
in Great Britain, 228
high-dose exposures, 4
in Kerala, India, 228
low-dose exposures, 4, 8, 31, 43
occupational exposures, 204
uncertainty in estimates, 3, 7
U.S. population exposure, 3
in Yangjiang County, Guangdong Province, China, 228
NBS gene, 80
Nbs1, 36
NBS1, 37
Nervous system
benign tumors, 152
cancer of, 148, 149, 151, 152, 171
Neural tube defects, 93
Neurofibromatosis, 80, 84, 92, 98
Neutrons
animal studies, 28-29, 68, 126
atomic bomb survivors, 20, 27, 142, 143, 146
carcinogenesis, 50
cell cycle effects, 50
cell killing, 28
chromosome aberrations from, 27-28
damage mechanisms in tissues, 19, 27
dose-effect relationship, 28
DS02 dosimetry, 27
high-energy, 19
leukemia, 71
linear dose coefficient, 28
and lymphoma, 68
mutations in mice, 68, 126, 127
occupational exposures, 199, 204
physics, 19
RBE, 20, 27-29, 126, 142, 143, 146, 297
weighting factor for absorbed dose, 296-297
Nevoid basal cell carcinoma syndrome, 80, 82, 83, 84
New York State Postpartum Mastitis Study, 26
NF2 gene, 80
NF-kappaB transcription factor, 51, 53
Nijmegen breakage syndrome (NBS), 79, 80, 81, 83
4-Nitroquinoline-N-oxide (4NQO), 75, 76
Non-Hodgkin’s lymphoma, 151, 157, 158, 162, 164, 171, 209, 227, 229, 231
Nuclear Electric, 190
Nuclear facilities.
See also Nuclear industry workers;
individual facilities
see Chernobyl accidents
commercial power plants, 3, 190
dosimetry in population exposures, 209-211, 212, 213, 214, 229-232
fuel processing plants, 190, 199-200, 209, 212, 213, 215, 229, 234
occupational exposures, 190
population exposures in proximity to, 208-215
U.S. population exposure to radiation from, 3, 5
Nuclear Industry Family Study, 233
Nuclear industry workers.
See also Occupational radiation exposure;
individual facilities and sites
age associations, 200
assessment of exposure, 193-194
atomic bomb survivors compared, 201, 203
bone cancer, 201
cancer incidence and mortality estimates, 191, 194-198, 200, 201, 202, 203
cesium-127 exposure, 202
Chernobyl liquidators, 57, 58, 60, 114, 129, 202-204, 226, 227
childhood cancers following parental preconception exposures, 229, 230-232, 233
chromosome aberrations, 57, 58
cohort characteristics, 191-193
commercial nuclear power facilities, 190
confounding factors, 136, 198, 199-200
design of studies, 138-139, 198
dosimetry, 60, 138-139, 190, 191, 192, 193, 198-199, 201, 202, 203, 231, 233, 290
epidemiological studies, 138-139, 189, 190-193, 233
healthy worker effect, 194
heavy metal exposures, 200
internally deposited radionuclides, 190, 193, 194, 199-200, 201
leukemia, 14, 190, 191, 196, 197, 198, 199, 200, 201, 202-204
liver cancer, 201
lung cancer, 135, 190, 198, 200, 201
at Mayak plutonium production complex, 13-14, 57, 190, 201-202
modifiers of radiation risk, 200-201
multiple myeloma, 197
mutations, 60
plutonium exposure, 190, 194, 199, 200, 201-202
pooled analyses of studies, 14, 191-193, 194-195, 198, 200
protracted exposures, 200-202
reproductive health, 233
risk estimates, 194-198, 203-204, 290
risk modeling, 138, 262, 268, 275, 290
Sellafield Nuclear Facility, 57, 58, 190, 192, 194, 195, 196, 197, 229, 230, 231
sensitivity of studies, 5-6
skin cancer, 190
smokers/smoking, 194, 198, 199
socioeconomic status, 199
solid cancers, 201
thyroid cancer, 203-204
uncertainties in data, 14, 194, 198
Nuclear medicine, U.S. population exposure from, 3, 5
Nuclear membrane damage, 29, 49
Nuclear Regulatory Commission (U.S.), 2 93
Nuclear weapons testing
Bikini test site, 234
British tests, 212, 213, 214, 235
Castle BRAVO, 214
multiple myeloma, 214
Nevada Test Site, 234
Operation HARDTACK, 213
Operation UPSHOT-KNOTHOLE, 6
participant exposures, 6, 212, 213, 214
population exposures, 3, 5, 6, 114, 212-215, 234, 276
Semipalatinsk test site, 114, 128-129
and thyroid cancer, 212, 215, 234, 276
Nucleotide pools, alterations in, 48
O
Oak Ridge National Laboratory, 190, 191, 192, 193, 194, 195, 196, 198, 200
Oak Ridge X-10 Plant, 191, 192, 195
Oak Ridge Y-12 plant, 190, 191, 192, 195, 200
Observational studies, defined, 133
Occupational radiation exposure.
See also Nuclear industry workers;
Radiation workers;
specific occupations and cohorts
airline and aerospace employers, 204
BEIR V report, 190
and cardiovascular disease, 199
confounding in, 136, 189, 194, 198, 199-200, 205
dose-response relationship, 189
epidemiological studies, 189-190
healthy worker effect, 189, 194, 205
medical and dental personnel, 189, 204-205, 266;
see also Radiologists and radiologicl technicians
monitoring, 189
Portsmouth Shipyard Study, 135, 136
and reproductive health, 5, 233
risk estimates, 280
sensitivity of studies, 5-6, 189
skin cancer, 2
types of, 189
uncertainty in, 14
Ocular albinism, 93
Oncogenes.
See also Proto-oncogenes;
Tumorigenesis, radiation induced
activation, 65
defined, 376
Oncovin, 130
Oocytes
chemotherapy effects, 130
primordial, 92
sensitivity to cell killing, 75, 98-99, 119
Oropharyngeal cancers, 148, 149
Osteogenesis imperfecta, 98, 103, 125
Osteopetrosis, 98
See also Bone cancer
Otosclerosis, 98
Ovarian carcinoma
in atomic bomb survivors, 147, 148, 149, 269
dose-response relationship, 12, 50
genetic susceptibility, 67, 69, 74, 75, 76
incidence, 298
mortality, 298
radiotherapy-related, 80, 84, 160, 164
risk models and estimates, 272, 278, 279, 280, 282, 285, 294, 303-306
Oxford Survey of Childhood Cancer, 10, 172-173
Oxidative stress
adaptive response to, 50
DNA damage, 19, 30-32, 34, 40-42, 50
Oxygen, and radiation resistance, 50
oxyR transcription factor, 50
P
p53, 35, 36, 37, 39, 48, 49, 53, 54
Pair-production process, 20-21
Pancreatic cancer, 147, 148, 149, 163, 164, 168, 204
Pantex, 190
Paracrine growth factors, 86
Paracrine proapoptotic or antiapoptotic factors, 54
Parathyroid cancer, 80
Parkinson’s disease, 153
Parotid gland, tumors of, 171
PCNA (proliferating cell nuclear antigen) protein, 32, 33, 39, 53
Peptic ulcer, 163, 174, 175, 185, 242, 287, 288
Peroxyl radicals, 31
Phenylketonuria, 93
Phosphatidyl-3-inosityl enzymes, 36
Phosphorylation
of histone protein, 36
of kinases, 37
Photo effect, 22
Photoelectric process, 20
Photons
absorption and scattering, 20-21
annihilation events, 21
defined, 376
linear dose coefficient, 28
penetration depth, 21
spectral distributions, 20-22
Photosensitivity, 80
Physical aspects of ionizing radiation
epidemiological studies, 24-26
experimental observations, 28-29
genetic damage mechanisms, 26-27
in vivo studies, 24
LET, 22-24
neutron interaction with tissue elements, 27-29
photon spectral distributions, 20-22
RBE, 22-29
types of radiation, 19-20
PI-3 kinase, 67
Plutonium-239, 20, 190, 194, 199, 200, 201
PMS1 and PMS2 genes, 60
Poly-ADP-ribose synthetase, 32, 33, 34
Polycystic kidney disease, 98
Polymerase β (POL β), 32, 33, 34, 35
Polymerase δ (POL δ), 32
Polymerase chain reaction, 127, 130
Polynucleotide kinase (PNK), 32, 33
Polyposis of intestine, 98
Porphyria, 98
Portsmouth Naval Shipyard Study, 135, 136, 191, 192, 197, 200
Postradiation generation progeny
first, 116
genetic disease risk, 116
mutations in, 70
second, 116
Potential recoverability correction factor (PRCF), 119
for autosomal dominant diseases, 110, 115, 119
for autosomal recessive diseases, 110-111, 115
BEIR V methods compared, 115
for chronic multifactorial diseases, 111, 115, 119
for congenital abnormalities, 111
estimates, 110
multisystem developmental abnormalities, 115
and revision of risk estimates, 109-110
strengths and weaknesses, 111, 119
weighted, 115
for X-linked diseases, 110, 115, 119
pRb, 39
Prednizone, 130
Pregnancy outcomes, adverse, 8, 131
Primary basilar impression, 98
Premature chromosome condensation techniques, 46
Prkdc gene, 71
Procarbazine, 130
Prolactin, 76
Prostate cancer, 147, 148, 149, 164, 200, 204, 269, 272, 278, 279, 280, 282, 298, 303-306
Prostate hyperplasia, 153
Protein kinases, 35-39, 51, 55
Protein-8 (XIP8), 56
Protracted exposure
and bone cancer, 75
and breast cancer, 176, 180, 243
and cancer risk assessment, 241, 243
and DNA damage, 31
dose-rate effects distinguished from, 77
genetic risk assessment, 92
radiation protection implications, 189
reduction in risk for, 246
thyroid cancer, 182
and tumorigenesis, 75
Protons
dose-effect relationships, 28
Proto-oncogenes, 66, 68, 80, 81-82
PTC gene, 80
5′,8-Purine cyclodeoxynucleosides, 34
Pyloric stenosis, 120
Pyrimidopurinone, 34
Q
Quality factor (Q)
basis for, 22
defined, 376
Quantitative studies
in experimental tumorigenesis, 73-79
R
RAD50, 37
RAD52, 38
RAD54, 38
Radiation Effects Research Foundation, 91, 140, 141, 142, 152, 267, 269, 270, 271, 285, 286, 296, 297, 298, 301, 302, 307.
See also Atomic bomb survivors;
Life Span Study
Radiation protection
dose units, xi
genetic susceptibility implications for, 85
photon energy considerations, 24
protracted exposures and, 189
quality factor, 22
RBE and, 276
Radiation quality.
See also Quality factor
LET as a measure of, 22-24
and mutation frequency, 47
Radiation resistance, 30, 32, 40-42
DNA repair, 49
priming dose and, 51
Radiation weighting factor, xi, 24
Radiation workers. See Nuclear industry workers;
Occupational radiation exposure
Radioisotopes.
See also specific radioisotopes
diagnostic exposures, 156
Radiologists and radiologic technicians
breast cancer, 205
colon cancer, 205
mortality rate, 2, 189, 204, 205
pancreatic cancer, 204
prostate cancer, 204
Radionuclides.
See also Internally deposited radionuclides;
specific radionuclides
in utero exposures, 330
organically bound, 330
in work environment, 199-200
Radiosensitivity
age and, 68
animal studies, 34, 69, 71, 82-83
of bone marrow, 173
cardiovascular system, 185-186
cell cycle phase and, 45, 49-50, 55, 82, 83, 86, 113
and cell killing/lethality, 55-57
DNA repair defects and, 32, 34, 37, 40, 56, 69, 71, 80, 82, 83, 87, 239
dose fractionation, 55
gene polymorphisms, 87
hypersensitivity to low doses, 11, 32, 45, 47, 51, 55-57, 71, 82, 239
sex differences, 119
Radiotherapy studies
ankylosing spondylitis cohort, 164-165, 174, 176, 177, 185
benign breast disease cohorts, 163, 174, 177, 180, 185
for benign diseases in adults, 155, 162-166
benign diseases in children, 155, 166-167, 181
benign gynecological diseases, 163-164
bladder cancer in recipients, 157, 158, 162, 163, 164
bone cancer in recipients, 157, 161, 162, 164, 167
brachytherapy recipients, 162
breast cancer patients, 26, 84, 86, 135, 157, 159-160, 164-165, 167, 168, 169, 174, 175, 176-180, 186-187, 205, 243
cardiovascular disease mortality, 159, 160, 185-187
cell killing, 155
cervical cancer survivors, 26, 135, 157-158, 174, 176, 177, 185
children, 9, 84, 156, 161-162, 166-170
chromosomal aberrations, 53
dose-response relationship for secondary cancer, 157-170
dosimetry, 155, 156-157, 159, 161, 176-177, 183, 184, 186, 187
extrapolation to other populations, 155
genetic effects, 9
Hodgkin’s disease patients, 130, 158-159, 174, 176, 177, 242-243
for hormonal infertility, 164
hyperthyroidism studies, 165-166, 169, 181, 185, 234
for malignant diseases, 9, 130, 155, 156, 157-162
and minisatellite mutations, 114, 130
mouse studies, 130
non-Hodgkin’s lymphoma patients, 162
occupational exposures, 205
ovarian cancer patients, 160
in peptic ulcer patients, 163, 174, 175, 185
postpartum mastitis cohorts, 26, 163, 177, 180
and radiosensitivity, 82, 83-87, 155
registries, 155
secondary tumors, 84-85, 86, 88, 135, 155, 157-162, 173-187
site-specific cancer risk estimates, 173-187
and skin cancer, 68
skin hemangioma cohorts, 168-169, 174, 175, 176, 177, 180, 181, 183, 185
testicular cancer patients, 160-161
thymus gland enlargement, 156, 167-168, 176, 177, 180, 181, 182
thyroid cancer patients, 161
thyroid diseases (benign), 165-166, 169
tinea capitis cohort, 68, 155, 156, 166-167, 181, 182, 183
tonsil enlargement cohort, 155, 169, 181
uterine cancer patients, 162
Radium-226, 163, 164, 168, 169, 183, 185, 209
See also Uranium miners
and lung cancer, 242
Randomized intervention trials, 133-134
Rare diseases (early onset), 98
RAS gene, 68
Rats
renal carcinoma in Tsc-2-deficient genotype, 69
tumor-suppressor-gene-deficient, 82, 83
Reactive oxygen species, 31-32, 40-42, 48
adaptive response to, 50
bystander effect, 54
Rectal cancer
in atomic bomb survivors, 147, 148, 149, 151
radiotherapy-related risks, 157, 158
Relative biological effectiveness (RBE)
alpha particles, 71
animal studies, 28-29
and cancer risk assessment, 276
cell cycle phase and, 50
and chromosome aberrations, 24, 27-28, 276
defined, 376
dose-rate effects on, 21, 24, 28
experimental observations, 28-29
gamma rays, 21, 22-24, 126, 276
and gene mutations, 47
and genomic instability, 71
LET of radiations and, 21, 24, 31, 47
neutrons, 20, 27-29, 126, 143, 146, 297
protracted exposure and, 75, 176, 180, 243
Relative risk, defined, 132, 376
Renal carcinoma, 69, 70, 80, 222
Research recommendations
atomic bomb survivor studies, 18, 317-319
baseline frequencies of Mendelian diseases, 316-317
biological phenomena at low doses, 9, 16-17, 314-315
bystander effects, 314
Chernobyl cleanup workers, 204
doubling dose calculations, 316
environmental radiation studies, 17-18, 321
epidemiological studies, 18, 317-321
genetic effects of radiation, 17, 316-317
genetic susceptibility to cancer, 17, 315
genomic instability, 49, 53, 315
hyperradiosensitivity for low doses, 314
integration of biology and epidemiology, 321-322
lifetime risk models, 322-323
medical radiation studies, 5, 17, 319-320
molecular and cellular responses to ionizing
multisystem developmental abnormalities, 317
occupational radiation studies, 17, 320-321
potential recoverability correction factor, 317
radiation-sensitive subpopulations, 314
tumorigenic mechanisms, 17, 315-316
whole-body CT scan cohorts, 5
Respiratory system cancer.
See also Lung cancer
atomic bomb survivors, 149, 292
Chernobyl accident and, 218
model, 292
Restricted LET
defined, 19 n.1
Retinal tumors, 80
Retinoblastoma, 80, 84, 98, 103, 125, 161
Rhesus monkeys, oocyte radiosensitivity, 99
Risk assessment.
See also Cancer risk assessment;
Genetic risk assessment;
Models/modeling
absolute risk, 260-261
BEIR I approach, 138
Committee approach, 6-9
confidence intervals, 133, 136, 137-139, 176
defined, 377
definition of risk, 260
excess risks, 132, 137-138, 260-261
incidence rates and, 259, 260-261
incomplete covariate information and, 265
lifetime risk projections, 137, 240, 264-265
mathematical models, 261-262
measures of risk, 132
pooling data from multiple studies, 169, 172
RBE in, 28
relative risk, 261
sample sizes, 297
validity of estimates, 266
Rochester Thymus Study, 26, 180, 181, 292
Rocketdyne/Atomics International, 191, 192, 194, 197, 200
Rocky Flats, 190, 191, 192, 193, 195, 196, 197, 199
Roentgen, Wilhelm Conrad, 1-2, 156
RPA, 38
Russell, William, 100 n.1
S
Saccharomyces cerevisiae, DNA repair in, 30, 36, 40-42
Sahlgrenska University Hospital, 168
Salivary gland tumors, 149-150, 161, 165, 167, 269
See also Osteosarcoma;
Soft tissue sarcoma
Sasakawa Foundation, 225
Schwannomas, 152
Scoliosis, 155, 172, 176, 177, 187
Searle, Tony, 100 n.1
SEER (Surveillance, Epidemiology, and End Results) registry, 242
Segmental aneusomy syndromes, 112
Sellafield Nuclear Facility workers, 57, 58, 190, 191, 192, 195, 196, 197, 198, 199, 200, 229, 230, 231, 233
Seminoma, 130
Semipalatinsk nuclear test site, human minisatellite loci mutations, 114, 128-129
Signal transduction pathways
DNA repair, 32, 34, 36-39, 48, 49, 54, 80
and dose-response relationships, 62
and genomic instability, 78
hypersensitivity to radiation and, 56
Sister-chromatid
Skeletal disorders, 80, 112, 115, 116.
See also Bone cancer
Skin cancer
age dependency, 298
animal studies, 74, 75, 76, 87
in atomic bomb survivors, 148, 149, 150-151, 269, 295
beta particles and, 75
caretaker gene, 67
dose-response relationship, 74, 76, 151, 245
excess relative risk, 148
fluoroscopy and, 2
gatekeeper gene, 66
genetic susceptibility to, 80, 84, 87
in radiologists, 2
radiotherapy-related risks, 84, 162, 167
risk estimates, 245, 270-271, 282, 294, 295
in tinea capitis radiotherapy patients, 68, 167
xeroderma pigmentosum and, 79
Skin hemangioma cohort, 26, 168-169, 172, 174, 175, 176, 177, 178, 180, 181, 183, 185, 287
Smoke detectors, 3
Smokers/smoking
and carcinogenesis, 242
confounding in radiation studies, 57, 138, 150, 198, 199, 242, 245
and liver cancer, 242
and lung cancer, 87, 135, 138, 150, 174, 176, 198, 242, 245
radiation exposure in tobacco, 3, 4
synergistic effects, 242
Socioeconomic status, confounding in radiation studies, 199
Soft tissue sarcoma, 80, 84, 161
Solid cancers, 6
age dependencies, 297-298
in atomic bomb survivors, 142, 143, 144-147, 245, 297-307
baseline risks, 241
Chernobyl accident and, 227-228
defined, 377
dose-response relationship, 74-75, 142, 144, 145-146, 201, 245, 298
medical-use-related risks, 161, 172, 287-289
mortality data, 144, 280, 298-307
murine studies, 74-75
risk assessment models, 143, 144-145, 241, 269-271, 279, 284, 287-289, 297-307
spontaneously occurring, 65, 66-67
sum-of-sites estimates, 279-280, 296
vasculature, 66
Somatic cells
defined, 377
DNA repair in, 36
mutagenesis in, 46-47, 66, 113, 127
tumorigenesis, 66
soxRS transcription factor, 50
Specific locus tests
dominant mutations in mice, 100-101
Spherocytosis, 98
Spondylosis, 165
Spontaneous mutations, 91
clusters, 97
dominant disorders, 97-98
doubling dose calculations, 8, 96-101, 119
estimation of rates, 97-98
extrapolation from mice to humans, 96-97
in genetic risk assessment, 96, 102, 109-111, 124-125
germinal mosaics, 97
in human genes, 96-98, 109-111, 124-125
mechanisms, 124-125
and natural selection, 94, 102
paternal age effects, 97
point, 47
radiation-induced damage compared, 30, 124-125
recoverability in live births, 109-111, 124, 125
sex differences, 96-97
Springfields nuclear workers, 191, 192, 195, 196
Squamous cell carcinoma, 67, 80, 151
Stanford University Medical Center, 159
State Chernobyl Registries, 203
Statistical methods
atomic bomb survivors, 143-144
inference tools, 137-138
Statistical power of studies, 136
Stem cell spermatogonia, 92, 98, 113, 119, 126, 127
Steroid hormone receptor genes, 86
Steroid sulfatase deficiency, 93
Stomach cancer.
See also Digestive system cancer
in atomic bomb survivors, 147, 148, 149, 150, 151, 215, 240, 242, 269, 288
baseline lifetime risk estimates, 278
in cervical cancer survivors, 158, 185, 288
childhood exposures and, 168, 185
etiology, 241-242
excess relative risk, 12, 287, 288, 289, 301-302
incidence, 173-174, 185, 278, 284, 298, 303, 305, 304, 306
radiotherapy-related, 12, 157, 159, 160, 163, 164, 166, 168, 185, 186, 287, 288, 289
risk models and estimates, 12, 173, 185, 186, 215, 269, 272, 275, 278, 279, 280, 282, 284, 285, 294, 301, 303-306
risk transport model, 241-242
Strontium-90, 212, 213, 214, 269, 276
Swedish benign breast disease study, 26
Swedish Cancer Registry, 166
Swedish Family Cancer Database, 88
Swedish infant skin hemangioma patients, 26
Synchrotron radiation, 24
T
Tcr gene, 68
TEC facility, 200
Televisions, 3
Telomere-like repeat sequence arrays, 69
Terrestrial radiation, 43
Testicular cancer, 160-161
12-O-Tetradecanolyphorbol-13-acetate (TPA), 75
Tetrapeptide repeats (TPRs), 52
Therapeutic irradiation. See Medical uses of radiation;
Radiotherapystudies
Thorium, 3
Three Mile Island, 208, 209, 211
Three-Country Study, 14
Thymine glycols, 52
Thymus gland enlargement, radiotherapy risks, 26, 167-168, 176, 177, 180, 181, 182, 243, 273, 287, 292
Thyroid cancer
age at exposure and, 74, 76, 86, 149, 167, 181-182
in atomic bomb survivors, 148, 149, 181, 244, 269, 295
benign thyroid nodules, 168, 244
in cervical cancer survivors, 181
Chernobyl accident and, 68, 72, 203-204, 215-226, 234-235, 246, 276
childhood exposure and, 68, 72, 149, 161, 162, 166, 167, 168, 169, 181, 182, 214, 215-226, 234, 244, 246, 287
chromosomal aberrations and, 67, 246
coherence of BEIR VII model with other studies, 287
diagnostic irradiation and, 171, 234
dose-response relationships, 149, 160, 162, 167, 168, 169, 182, 215, 224, 225, 276
ethnic origin and, 167
etiology, 244
excess relative risk, 12
familial medullary, 80
genetic susceptibility, 80, 81-82, 86, 244, 246
hormones and, 244
in utero exposure and, 224, 225
iodine deficiency and, 225, 244
iodine-131 exposure and, 12, 68, 161, 165, 171, 182, 213, 215-226, 233-235, 276
latent phase, 215
medical-exposure-related risks, 12, 161, 180-182, 234, 287
model, 273
multiplicative model, 244
nuclear facility proximity and, 213, 215, 234, 276
nuclear weapons tests and, 212, 234, 276
papillary, 68
pooled analyses or risks, 181, 268, 287, 295
radiosensitivity of thyroid gland, 173
radiotherapy-related risks, 157, 159, 161, 162, 166, 167, 168, 169, 181-182, 234
relative risk, 244
risk assessment, 181, 244, 268, 270-271, 272, 273, 275, 282, 286, 287
risk estimates, 173, 180-182, 282, 294
risk factors, 244
sex differences, 161, 167, 181, 244
Thyroid diseases
dose-response relationship, 153
radiotherapy-related risks, 165-166, 169
Thyroid stimulating hormone, 244
Thyrotoxicosis, 166
Tinea capitis cohorts
pooled data for risk assessment, 273
radiotherapy-related risks, 68, 155, 156, 166-167, 181, 182, 183
skin cancer, 68
Tobacco, 3.
See also Smokers/smoking
Tonsil enlargement, 169
Topoisomerase, 34
TP53 gene, 67-68, 79, 80, 81, 82, 83
Tradescantia, 24
Traits, heritability of, 106
Transcription factors, 51, 53, 66, 67
Transforming growth factor-α (TGF-α), 55
Translocations
cell cycle phase and, 45
dose-response relationships, 57, 58, 60, 61
nonreciprocal, 48
segmental jumping, 72
telomeric sequences at, 72
Trichothiodystrophy, 80
Triliated thymidine (3HTdR), 53, 55
Tritium, 200
TSC1 gene, 80
Tuberculosis patients. See Fluoroscopy
Tuberous sclerosis, 80, 82, 83, 98
Tumor progression, 49
action of, 241
and dose-response relationships, 75, 76
environmental/lifestyle factors, 242, 244, 254
stomach cancer, 241-242
Tumor registries, 141, 142, 147-148, 150, 151, 152
Tumor suppressor
genes, 39, 65, 66, 67-68, 69, 80, 80, 81, 82-83
Tumorigenesis, radiation induced
adaptive responses, 12, 51, 52, 62, 78-79, 250-251
aggressive, 72
alpha particles and, 70
animals studies, 11, 12, 67, 68-70, 73-79, 82-83, 89, 240
cell killing and, 12, 74, 75, 76, 82
chromatid instability and, 70-73
chromosome aberrations and, 24, 46, 66, 68-69, 70, 72-73, 74, 82, 86
confounding stress factors, 71
diet and, 242
DNA damage response and, 6, 11, 65, 68, 69, 70, 73, 82, 83, 239, 227-228, 239, 246
dose-response relationships, 12, 45, 50, 55, 59, 60, 61-62, 68, 70, 73-77, 84, 89, 140, 245-246
epidemiologic studies, 68
etiology at different histologic sites, 241-245
fractionation kinetics, 73, 75-76, 78-79, 182
genetic susceptibility, 12, 65-66, 79-90
genomic instability and, 11-12, 39, 49, 65, 66, 67, 69, 70-73
in hematopoietic cells, 70-71
life-span shortening, 76-77
lymphoma and leukemia, 68-70, 71, 73-74
malignant transformation, 51-52, 62, 78-79
mammary epithelial cells, 71-73
mechanisms, 11-12, 27, 65, 66-70, 74, 75, 76, 81-82, 89, 245
monoclonal origins, 11, 245, 253-254
persistence of initiated cells postirradiation, 76
phases and process, 11, 66, 240
in progeny, 70
quantitative studies, 73-79, 89
solid tumors, 74-75
spontaneous mechanisms compared, 11, 12, 66-67, 70, 239
target for, 54
telomere sequence instability and, 12, 71-73
temporal projections of risk, 239-240
UV radiation and, 67-68
Twin studies
of genetic susceptibility to cancer, 88
of multifactorial diseases, 93
U
Ulcer patients
dose-response relationship, 153
radiotherapy-related cancer risk, 163
Ultraviolet light
DNA damage, 40
Uncertainties.
See also Bias;
Confounding factors
from age-related effects, 297
in atomic bomb survivor data, 130, 131, 141, 147, 172, 285-286
cancer risk estimates, 25-26, 147, 174, 251, 268, 272-273, 275, 276, 278, 279, 280, 284-286, 297, 308-310
in Chernobyl data, 128, 129, 202-203
chromosomal radiosensitivity, 82
combining sources of, 309-310
in cross-population transport, 279, 284, 285, 286, 296
in DDREF, 279, 284, 285, 286, 295, 296, 310
defined, 377
in diagnostic radiation risk estimates, 286
in dose-response relationships, 246
in dosimetry, 3, 14, 128, 129, 139, 142, 169, 198-200, 233, 241, 266, 285
in doubling dose estimates, 98-99, 130, 131
EPA assessment of, 284
in epidemiological studies, 133, 284
in error correction, 296
in exposure estimates, 114, 174
in genetic risk estimates, 98-99, 114
joint analysis, 295
LAR analysis, 278, 279, 284, 308-310
in lifetime cancer risk, 278, 279, 284-286
Monte Carlo analysis, 293, 295
NCRP assessment of, 284
occupational exposures, 14, 194, 198
in population effects, 286
procedures for addressing, 308-310
quantitative evaluation, 278, 284-285
in radiation exposure data, 3, 169
in risk estimates, 29, 284, 286
from sampling variability, 278, 279, 280, 284, 285, 296, 308-309
statistical, 29
time since exposure, 275
Underground miners. See Uranium miners
United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), 91, 93
cancer risk model, 138, 240, 268, 272, 274, 275, 277-278, 282-283, 293-294, 297-298, 307
congenital abnormality frequencies, 112
defined, 377
genetic risk calculations, 92, 94, 95, 96, 109, 111, 112, 118, 131
lifetime cancer risk estimates, 294
mutation rate estimation, 109, 111
occupational exposure studies, 190
United Nuclear Corporation, 190
Uracil, 30
Uranium miners, 190
risk modeling, 262
Urinary tract cancer.
See also Bladder cancer
ankylosing spondylitis cohort, 164
atomic bomb survivors, 148, 149
cervical cancer survivors, 157, 158
Chernobyl accident and, 223, 227-228
U.S. Department of Energy, nuclear facilities, 190, 198
U.S. Environmental Protection Agency (EPA), 274, 275, 282, 283, 293, 294
U.S. Food and Drug Administration, 5
U.S. Scoliosis Cohort Study, 172
Uterine bleeding disorders (benign), 163-164, 183, 287, 288
Uterine cancer
in atomic bomb survivors, 147, 148, 149, 269, 298, 303-306
radiotherapy-related, 157, 158, 159, 162, 163, 287
risk models and estimates, 272, 278, 279, 280, 282, 303-306
Uterine fibroma, 86
V
Vaginal cancer, 157
Varicose veins, 95
Vinblastine, 130
Vincristine, 130
Von Hippel-Lindau syndrome, 80, 125
W
Warthin’s tumor, 150
Water, electron ionization, 21, 29-32
World Health Organization, 128
X
Xenon, 209
Xeroderma pigmentosum, 79, 80, 81
X-linked disorders, 79
XPV gene, 80
X-rays.
See also Radiotherapy studies
animal studies, 68, 69, 100-101
atomic bomb explosion, 22
bystander effects, 54
cancer risk estimates, 171, 276
childhood exposures, 211
chromosome aberrations, 48, 86
correction to gamma rays, 24
defined, 378
diagnostic, 3, 4, 5, 6, 21, 22, 156, 171;
see also Mammography
discovery and early studies, 2