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(PP013) Radiation reveals the biological structure-function relationships.
ABSTRACT- In this study a model considering possible different modes of action of low and high-LET particles is tested against the data of experiments on cancer induction by ionizing radiation in rat skin. The multiple steps in completion of degeneration in genes, namely oncogenes and tumor suppressor genes on both chromosomes, biological repair of premutagenic damages, necrotic and apoptotic cell deaths, and proliferation due to cell death are also included in the model. The model predicts the possibility of two distributions of tumor occurrence during lifetime of the animals. The first distribution would represent cells that experienced mutational events in both chromosomes during irradiation. The second, later distribution might be expected from cells that acquired mutations in one of the chromosome during irradiation and then mutations on the other chromosome later due to natural processes. Experimentally distributions were distinct for the developmental and younger age animal groups. The first distribution was centered at about 400 days, while the second one at about 700 days of age. The dose-response relation from the model for electron radiation (low LET) included the second, third and fourth powers of the dose and for neon and argon ion radiation (high LET) the first, second and third powers. The fit of the data to dose-response relationships, which does not include the first power of dose for 0.8 MeV electron exposure clearly indicates that there is a strong repair of damage induced by low LET particles of lower energy at lower doses. Analyses disclosed that exposure to particles of different energy and LET show different cancer incidence dependence on the power of dose. Radiation with its different modes of action is a unique agent that reveals the effect of biological structure-function relationships on dose and time responses in carcinogenesis.
Key words: biological structure-function relationships, mutation, cancer, dose-response relationships
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