Induction of hepatic cell proliferation and unscheduled DNA synthesis in mouse hepatocytes following in vivo treatment.

We have modified the in vivo-in vitro hepatocyte DNA repair assay for measurement of unscheduled DNA synthesis (UDS) and hepatic cell proliferation in B6C3F1 mice. Dimethylnitrosamine and methylmethane sulfonate produced significant increases in UDS in both rats and mice. 2-Acetylaminofluorene induced a significant increase in UDS in rats, but not in mice. The mouse hepatocarcinogens, carbon tetrachloride, trichloroethylene, polybrominated biphenyls and 2,6-dichloro-p-phenylenediamine all failed to induce UDS in male and female mice, but all induced significant elevations in hepatic cell proliferation. Increased cell turnover in the liver may therefore be an important mechanism in hepatocarcinogenicity in the mouse.