Fundamental carcinogenic processes and their implications for low dose risk assessment

Various possible models of carcinogenesis are analyzed with respect to low dose kinetics. The importance of background carcinogenesis upon the shape of the dose-response curve at low dose is emphasized. It is shown that, if carcinogenesis by an external agent acts additively with any already ongoing process, then under almost any model the response will be linear at low dose. Measures of the degree of linearity are obtained for multistage models of carcinogenesis, where it is shown that throughout the dose range where the extra risk is less than the spontaneous risk linear extrapolation must be quite accurate.