Role of chemically induced cell proliferation in carcinogenesis and its use in health risk assessment.

There is much interest in incorporating knowledge of biological mechanisms of carcinogenesis into assessments of health risks to humans posed by chemicals in the environment. Debate over the soundness of using data from animal bioassays conducted at minimally toxic doses or fractions thereof for predicting cancer risks to humans exposed to much lower doses has stimulated interest in the question of whether genotoxic or mitotic effects predominate in chemical carcinogenesis. Cell division plays a key role at each stage in the evolution of cancer, and it is well documented that increased rates of cell proliferation can escalate the risk of malignancy. This article examines the current understanding of both mechanisms by which chemicals provoke cell proliferation and the contribution of various kinetic patterns of cell proliferation to carcinogenesis.