Health Effects of Exposure to Low Levels of Ionizing Radiations Time for Reassessment? (1998) / Chapter Skim
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6. Mathematical Models of Radiation Carcinogenesis
6. Mathematical Models of Radiation Carcinogenesis
Pages 41-50
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From page 41... ...
6 MATHEMATICAL MODELS OF RADIATION CARCINOGENESIS One recent development in radiation-protection research that has implications for risk assessment is the use of mathematical models of the cancer process based on a multistage mechanism. The concept of the multistage process of cancer dates back to the early part of the century, but it was in the 1950s that approaches to modeling the process gained momentum with the models developed by Armitage and Doll (1954, 1957)
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lead to some quantitative differences in analyses, a global description that covers the essence of the mode} can be used to gain an insight into the cancer process and derive some generally applicable implications. A schematic representation of the two-mutation mode!
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thus incorporates the various steps associated with the development of cancer, such as initiation, promotion, conversion, and progression; but the terminology and characterization of these steps are not unambiguously identified in the cancer literature. The mathematical equations that can be derived from the mode} to describe the age-dependent incidence of a specific cancer do not always have an explicit solution, but by calculating the number of cells in each compartment-that is, the stem cells, the intermediate cells, and the malignant cells-for small intervals in an iterative process 43
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Thus, in accordance with cellular radiation biology a linear-quadratic dose-effect relationship might be used for the cellular effects of an acute exposure in general, with a linear dose-effect relationship for chronic and very protracted exposures; in addition, the cellular RBEs of different kinds of radiation can be taken into account. Radiation is normally not assumed to act as a promoter except at very high acute doses, when cell depletion might stimulate increased division of stem cells and intermediate cells.
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has therefore been used by some investigators to provide a basis for lifetime extrapolations of radiation risk. A BETR VTI phase-2 committee should examine all relevant models and consider how appropriate models might contribute to risk assessment.
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In all calculations, it was assumed that cellular radiation sensitivity was constant throughout lifetime and that the radiation sensitivity was equal for both mutational steps. If the exposure is over a lifetime, the mode!
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Because the background cancers must arise from "spontaneous" mutations, and there is interplay between the radiation-induced mutations and the "spontaneous" mutations, the mode! predicts that the risk following exposure to radiation depends on the background incidence of cancer associated with both acute and protracted exposures (figure 8~.
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Initial slope increases as spontaneous-cancer incidence increases. All calculations assume 48
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Initial slope increases as spontaneous-cancer incidence increases; both curves exhibit slight upward curvature. In all calculations, it was assumed that cellular radiation sensitivity was constant throughout lifetime and that the radiation sensitivity was equal for both mutational steps.
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that can be used to relate the molecular investigations on radiation mechanisms at the cellular level to the epidemiologic studies of exposed populations. The models also might provide a basis for extrapolating radiation effects to low doses and low dose rates and across populations which could be users!
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