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II Cellular Radiobiology
Pages 415-429

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From page 415...
... Molecular and cellular radiobiology have contributed greatly both to our understanding of the physical and chemical processes involved in the induction of radiation effects and to our understanding of the responses observed in whole organisms. Mom the vast store of radiobiological information, it is possible to draw a number of general principles.26 28~35~36 These principles sometune constitute our only rational basis for making human risk assessments, for example, when direct empirical observations on which to base such assessments are not available.
From page 416...
... Mutation induction in simple prokaryotic cells is an example of linear response, and the induction of two-break chromosomal aberrations of the exchange type in higher eukaryotic cells exposed to acute doses of low-LET radiation is an example of quadratic response. Many dose-response curves, however, are somewhere in between.
From page 417...
... It was noticed early, however, that when low-LET doses were protracted or appreciable periods passed between successive dose fractions, the effectiveness of the total dose was likely to diminish. In fact, as dose rate decreased, the radiobiological endpoints that at higher dose rates had response curves with an appreciable ,BD2 term began to lose that term.
From page 418...
... For the induction of radiobiological effects in mammalian cells, the target volume appears to be large enough for the effect to occur at a higher LET, with the maximally eRective LET being around 100 keV/,um. MICROSCOPIC DOSE DISTRIBUTION With energetic photon irradiation, the quantity dose, used in calculating a dose-effect model, has an easily understood meaning and is easy to measure empirically.
From page 419...
... However, as the fraction of cells hit approaches unity, the absorbed dose to the cell population can increase only if the number of hits per cell increases.8 At high doses and high dose rates, where each cell has received many hits, the variance of the mean decreases; so the dose to each cell, the mean dose to the cell population, and the mean dose to the organ or other medium approach equality. The other model that belongs in this category and that combines some elements of hit theory with those of microdosimetry is under development.8 The unique addition is an empirically derived hit size effectiveness factor.
From page 420...
... However, we can derive several generalizations that can be applied to the problem of extrapolating available empirical evidence of the induction of human health effects by low-LET radiation. First, even though the question of whether the low-LET effects best fit a simple linear dose-response model or a dose-squared model is unsettled, as far as the epidemiological data on radiation carcinogenesis are concerned (see Committee on the Biological Effects of Ionizing Radiations WEIR
From page 421...
... Although the appropriate RBE for a given alpha particle might not have been empirically measured in an appropriate target-cell system, generalizations on the basis of LET seem reasonable, provided that they are based on RBEs determined in cells likely to have similar cell nucleus and target volumes and based on doses that produce similar hit fractions per red. Thus, in considering the hazard of induction of a malignancy of, say, the liver by deposition of plutonium, it seems reasonable to multiply the low-dose risk coefficients for low-LET radiation available in the BEIR III report38 by an appropriate RBE factor to derive a new estimate that can be useful in the absence of empirical information on the overall risk associated with the radionuclide of interest.
From page 422...
... Because of the difference in survival-curve shapes, RBE was a function of the survival fraction at which the comparison was made with the reference curve, in this case for 25~kV x rays, peaking at about 9 for 80% survival and falling to approximately 3 at 0.001% survival. Blakely et al.7 recently reviewed extensive mammalian cell-survival studies with heavy ions, t2C to 40Ar, which used a variety of tissue-culture cell types.
From page 423...
... TRANSFORMATION IN VITRO A few types of mammalian cells growing in tissue culture can be transformed in vitro from the growth patterns that characterize fairly normal cultured cells to a new phenotype that more closely resembles that of cancer cells. The basic change is from an orderly growth pattern exhibiting contact inhibition on the culture vessel surface to a pattern resulting from the loss of contact inhibition.
From page 424...
... The role of DNA as a target in radiation transformation was suggested early by the requirement of DNA metabolism for fixation of the transformed state.~5 The ability of genomic high-molecula~-weight DNA purified from cells transformed In vitro to transmit the transformed phenotype to normal cells constitutes an important criterion for the neoplastic state of the cells transformed after exposure to a carcinogen, ~ 3~7~8~4t indicating that the transformed phenotype of the cells exposed to the carcinogen in vitro is encoded in the DNA. This criterion aids in mechanistic studies of transformation that attempt to analyze the specific transforming genes activated as a result of exposure to the carcinogen and to elucidate genetic changes.~7~'~ For both low- and high-LET radiation, transformants are produced as a function of increasing dose up to approximately 1-S surviving cells/100 exposed cells, at which point the curves saturate.
From page 425...
... (C) Focus of C3H/lOT-1/2 cells transformed by x rays growing over normal cells.
From page 426...
... However, the RBE for alpha transformation in nonproliferating cells appeared to be much higher; the yield of transformants among x-irradiated cells that were held in the stationary phase of growth for 0220 h after irradiation declined by a factor of nearly 50, whereas no decrease occurred in alpha-irradiated cells. The findings suggest that carcinogenic damage induced by high-LET radiation in mammalian cells is very inefficiently repaired, compared with that induced by x rays, and that the intracellular carcinogenic effect of exposures to high-LET radiation can be cumulative.
From page 427...
... 1980. Malignant transformation in cultured hamster embryo cells produced by x rays, 430-KeV monoenergetic neutrons, and heavy ions.
From page 428...
... 1979. Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions.
From page 429...
... 1979. Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions.


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