Extrapolation of carcinogenic risk from animal experiments to man. Environ health perspect 22

When estimating the absolute risk of cancer, the shape of the dose-response curve in the region of doses where actual exposure of man occurs is of crucial importance. This shape is equally important for the determination of relative risks, as in the comparison of risks from alternative energy sources. Experimen-tal and epidemiologic studies are, for various reasons, unable to give sufficiently exact information concerning the dose response in the low dose region. Therefore, the discussion concerning dose-response relationships also has to consider biologically reasonable mechanisms for the origin of tumors. Mutation Hypothesis Although it is realized that the development of cancer is a two-step or multistep process, the cur-rent hypothesis concerning the origin of cancer as-sumes that one or a few mutational events are in-volved in the initiation of tumors (1). This hypothesis is supported not only by the strong, qualitative correlation between mutagenic and car-cinogenic activities of chemicals but also by certain reaction-kinetic considerations, viz., a favoring of both the carcinogenic and the mutagenic potential by a relatively high reactivity towards certain cen-ters in DNA such as guanine-06 (2). In one case, the role in cancer initiation of a well-defined chemi-cal change in the DNA, the ultraviolet-induced thymine dimer, has further been described (3)