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 repairassay for measurement of unscheduled DNA synthesis (UDS) andhepatic cell proliferation in B6C3F1 mice. Dimethylnitros-amineand methylmethane sulfonate produced significant increases inUDS in both rats and mice. 2-Acetylaminofluorene induced a significantincrease in UDS in rats, but not in mice. The mouse hepatocarcinogens,carbon tetrachloride, trichloroethylene, polybrominated biphenylsand 2,6-dichloro-p-phenylenediamine all failed to induce UDSin male and female mice, but all induced significant elevationsin hepatic cell proliferation. Increased cell turnover in theliver may therefore be an important mechanism in hepatocarcinogenicityin the mouse.