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Solid tumor risks after high doses of ionizing radiation.

ABSTRACT: There is increasing concern regarding radiation-related second-cancer risks in long-term radiotherapy survivors and a corresponding need to be able to predict cancer risks at high radiation doses. Although cancer risks at moderately low radiation doses are reasonably understood from atomic bomb survivor studies, there is much more uncertainty at the high doses used in radiotherapy. It has generally been assumed that cancer induction decreases rapidly at high doses due to cell killing. However, recent studies of radiation-induced second cancers in the lung and breast, covering a very wide range of doses, contradict this assumption. A likely resolution of this disagreement comes from considering cellular repopulation during and after radiation exposure. Such repopulation tends to counteract cell killing and accounts for the large discrepancies between the current standard model for cancer induction at high doses and recent second-cancer data. We describe and apply a biologically based minimally parameterized model of dose-dependent cancer risks, incorporating carcinogenic effects, cell killing, and, additionally, proliferation/repopulation effects. Including stem-cell repopulation leads to risk estimates consistent with high-dose second-cancer data. A simplified version of the model provides a practical and parameter-free approach to predicting high-dose cancer risks, based only on data for atomic bomb survivors (who were exposed to lower total doses) and the demographic variables of the population of interest. Incorporating repopulation effects provides both a mechanistic understanding of cancer risks at high doses and a practical methodology for predicting cancer risks in organs exposed to high radiation doses, such as during radiotherapy.

SUBMITTER: Sachs RK

PROVIDER: S-EPMC1199000 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Understanding the effects of ionizing radiation (IR) on plants is important for environmental protection, for agriculture and horticulture, and for space science but plants have significant biological differences to the animals from which much relevant knowledge is derived. The effects of IR on plants are understood best at acute high doses because there have been; (a) controlled experiments in the field using point sources, (b) field studies in the immediate aftermath of nuclear accidents, and (c) controlled laboratory experiments. A compilation of studies of the effects of IR on plants reveals that although there are numerous field studies of the effects of chronic low doses on plants, there are few controlled experiments that used chronic low doses. Using the Bradford-Hill criteria widely used in epidemiological studies we suggest that a new phase of chronic low-level radiation research on plants is desirable if its effects are to be properly elucidated. We emphasize the plant biological contexts that should direct such research. We review previously reported effects from the molecular to community level and, using a plant stress biology context, discuss a variety of acute high- and chronic low-dose data against Derived Consideration Reference Levels (DCRLs) used for environmental protection. We suggest that chronic low-level IR can sometimes have effects at the molecular and cytogenetic level at DCRL dose rates (and perhaps below) but that there are unlikely to be environmentally significant effects at higher levels of biological organization. We conclude that, although current data meets only some of the Bradford-Hill criteria, current DCRLs for plants are very likely to be appropriate at biological scales relevant to environmental protection (and for which they were intended) but that research designed with an appropriate biological context and with more of the Bradford-Hill criteria in mind would strengthen this assertion. We note that the effects of IR have been investigated on only a small proportion of plant species and that research with a wider range of species might improve not only the understanding of the biological effects of radiation but also that of the response of plants to environmental stress.

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Solid tumor risks after high doses of ionizing radiation.

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