Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII Phase 2 (2006) / Chapter Skim
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2 Molecular and Cellular Responses to Ionizing Radiation
2 Molecular and Cellular Responses to Ionizing Radiation
Pages 43-64
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From page 43... ...
. Considissue of cellular effects at low doses of low-LET (linear en- ering the levels of background radiation, the maximal perergy transfer)
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As the dose is DDREF is used to estimate effects for either low doses or reduced, the term becomes less important, and the dose- low dose rates. This value for DDREF can be estimated from response relationship approaches linearity with a slope of .
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. Modeling procedures of this type, while ling evidence that the induction and interaction of DNA providing a coherent explanation of low-LET dose-response, double-strand breaks (DNA DSBs or, more correctly, are insufficient to account fully for high-LET effects double-stranded lesions)
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strong molecular evidence that in most circumstances, a Another important feature of the chromosomal response DNA deletion mechanism dominates mutagenic response to radiation is the postirradiation period during which initial after ionizing radiation (Sankaranarayanan 1991; Thacker DNA damage is fixed and then expressed in the form of 1992) , and it is for this reason that the genetic context of the aberrations such as dicentric chromosomes.
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. If, as molecular data suggest, error-prone NHEJ repair of There is controversy, however, as to whether all of these DNA DSBs is the principal source of radiation-induced gene different end points represent the same fundamental chromutations, then a linear dose-response would be anticipated mosomal alterations that result in genomic instability (Chang at low doses.
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. However, as reported recently (Hut and allows additional time for repair of DNA damage or, alternaothers 2003)
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phocyte cultures that were irradiated under different dose- Those effects have been observed in connection with relarate and mitogen-treatment conditions, postradiation incu- tively high acute doses of 1.510 Gy (1500-10,000 mGy) , bation allowing apoptotic processes to remove damaged cells but how such variations in radiosensitivity during the cell did not prevent the development of chromosomal instability cycle may affect responses to low doses up to 100 mGy is during long-term cell proliferation over 5157 days not known.
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. Similar obmin for mouse spermatogonia and 10 mGy/min for cells servations were reported for neoplastic transformation of in vitro is not caused by variations in radiosensitivity during C3H 10T1/2 cells by low-LET radiation, for which the dosethe cell cycle but rather by a diminished activation of error- response relationship for a low dose rate of 1 mGy/min was free repair at very low dose rates inasmuch as the rate of much below that observed for an acute high dose rate of induced DNA damage (signal)
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When mouse embryos were exposed to a noted that the base-excision repair enzymes involved in the priming dose of about 10 mGy and evaluated for chromoremoval of oxidative damage are not induced by low doses somal aberrations or defects in development induced by a of ionizing radiation in human cells (Inoue and others 2004)
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. HSP70 family by low doses of radiation (Sadekova and
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reporting that an average ocpression, which is modulated by p53 in response to radia- cupational exposure of about 2.5 mGy per year over 7 tion, may play an important role in regulating and coordinat- 21 years resulted in a variable adaptive response for chroing cell cycle progression, DNA replication, translesion mosomal aberrations induced in human lymphocytes by a synthesis, and DNA excision repair, depending on its part- large challenge dose of 2 Gy also reported that the incidence ner proteins. Within minutes after ionizing radiation, the of spontaneous aberrations was increased significantly by immediate-response genes transcription factors such as c- the occupational exposure.
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. Activation of the p53-mediated DNA damage particle traversal through an irradiated cell was lower by a response pathway in bystander cells has led to speculation factor of 35 than the direct effect on the irradiated cell and (Grosovsky 1999)
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suggest that HRS may be related to similar observation was reported for normal human diploid cells not arresting in radiosensitive G2. Since a high proporlung fibroblasts exposed to low doses of -particles; the tion of the target stem-like cells in humans would be observed enhancement of cell growth was hypothesized to noncycling G0 cells (see Chapter 3, "General Aspects of result from an ROS-caused increase in TGF- (Iyer and Dose-Response")
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Dashed line indicates basal level in untreated controls; ionizing radiation is a modest effect that has been detected solid lines were fitted by linear regression through the data. only in some, but not all, human cell lines investigated.
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and for Mayak misrepair of DNA damage had occurred (released from nuclear workers exposed over 15 years (0.50.9 × 10 / 5 confluence after potentially lethal damage repair had mGy for translocations; Burak and others 2001)
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curvature linear dose-response for LDR (Cornforth and others 2002) Human primary fibroblasts in G0-0.5 or Chromosome 3006000 Linear 4.9 × 105 LNT > 300 mGy 1 mGy/min aberrations (LDR)
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NOTE: LDR = low dose rate; PCC = premature chromosome condensation; PHA = phytohemagglutinin. aAcute indicates that doses were delivered at high dose rate (e.g., 0.1 Gy/min.)
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, the DDREF was 35 for acute doses at a low dose rate of 1000 mGy/d (0.69 mGy/min) or greater than 3 Gy and about 1.5 for acute doses less than 1000 mGy per week (0.1 mGy/min; Lorenz and others 2 Gy (Figure 2-8)
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. A malignant transformation experiment with primary hamster embryo cells exposed to five different doses from 0.03 to 1.5 Gy yielded a linear dose-response curve that had a slope of 4 × 10 transformants per viable cell per milligray 6 (Borek and others 1983)
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As has been pointed out dose exposures includes people who in the past have received (Cornforth and Bedford 1983) , a macroscopic X-ray dose of up to 500 mGy, the committee has focused on evaluating about 5 mGy would, on the average, result in one to two radiation effects in the low dose range of <100 mGy, with electron tracks crossing the nucleus of each cell.
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Until molecular genomic instability induced in X-irradiated cells and the fre- mechanisms of the bystander effect are elucidated, especially quencies of chromosomal aberrations induced directly by as related to an intact organism, and until reproducible byirradiation may suggest that the induction of chromosomal stander effects are observed for low-LET radiation in the aberrations is a primary event that plays a major role in dose range of 15 mGy, where an average of about one elecradiation-induced genomic instability. There is also some tron track traverses the nucleus, a bystander effect of lowevidence that reactive oxygen species may play a role.
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From page 64... ...
Most important, it is not known induction of genomic instability. Thus, the question of the if HRS plays a role when radiation doses <100 mGy are de- shape of the dose-response relationship up to about 20 mGy livered over weeks to months, which could be relevant for remains, although several of the dose-response relationships low doses of low-LET radiation.
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