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Dose-response relationships of genotoxic agents differ greatly depending on the agent and the endpoint being evaluated. Simple conclusions that genotoxic effects are linear cannot be applied universally. The shape of the molecular dose of DNA adducts varies from linear, to supralinear, to sublinear depending on metabolic activation and detoxication, and repair of individual types of DNA adducts. For...
Vinyl chloride produced several tumor types among species. Angiosarcoma of the liver is found in all tested species, including humans with occupational exposures. Vinyl chloride is biotransformed by CYP2E1 to DNA-reactive chloroethylene oxide producing cyclic etheno adducts, which are mutagenic. The dose-response for angiosarcoma of the liver formation in rodents is supralinear, which is consistent...
Biotransformation of chemical carcinogens involves both metabolic activation and detoxication. The molecular dose present on DNA as adducts represents a balance between these two pathways (formation) and DNA repair. All of these are enzymatic processes subject to saturation. When none of the pathways is saturated, linear molecular dosimetry is expected, whereas if metabolic activation is saturated,...
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