ABSTRACT
The basis for the short-term testing approach is derived from observations and carcinogenesis studies that indicate that the induction of many cancers can be traced to chemical exposures which cause mutational events. In experimental animal models, initiation of the target cell population is caused by the administration of single, small “initiating” doses of carcinogen. The binding of the carcinogen to the DNA of the cell is an irreversible event whose effectiveness is dependent upon how soon lesion is “fixed” by cellular replicative DNA synthesis. By combining different cell types and genetic endpoints, the potential genotoxicities of diverse classes of chemicals is determined. The influence of factors such as age, sex, cell type, organ, species, and other variables on genotoxicity can also be elucidated by choosing the appropriate combination of activating and target cells. According to current understanding of chemically induced carcinogenesis, it was premature to expect that one in vitro mutagenesis test could have the predictive power for chemical carcinogenicity.
