Article

A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: Approach

Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA.
Biophysik (Impact Factor: 1.58). 07/2009; 48(3):263-74. DOI: 10.1007/s00411-009-0230-3
Source: PubMed

ABSTRACT Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long-term models is needed. As an example of this novel approach, we integrate a stochastic short-term initiation/inactivation/repopulation model with a deterministic two-stage long-term model. Within this new formalism, the following assumptions are implemented: radiation initiates, promotes, or kills pre-malignant cells; a pre-malignant cell generates a clone, which, if it survives, quickly reaches a size limitation; the clone subsequently grows more slowly and can eventually generate a malignant cell; the carcinogenic potential of pre-malignant cells decreases with age.

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