The Hepatocyte Primary Culture/DNA Repair Assay Using Mouse or Hamster Hepatocytes

The hepatocyte primary culture (HPC)/DNA repair assay using rat hepatocytes was developed to identify genotoxic chemicals. Since there are species differences in susceptibility to chemical carcinogens, it was desirable to extend the assay to other species. Carcinogens and noncarcinogens from six structural classes were tested with hepatocytes from B6C3F1 mice or Syrian hamsters. In hepatocytes from both species, DNA repair was elicited by the carcinogens methyl methanesulfonate, aflatoxin B1, 2-acetylaminofluorene, benzo(a)pyrene, dimethylnitrosamine, nitrosopyrrolidine, 3'-methyl-4-dimethylaminoazobenzene, and p-dimethylaminoazobenzene. With aflatoxin B1, mouse hepatocytes required a dose of 10(-4) M for a maximum response while only 10(-6) was needed for hamster hepatocytes. All the presumed noncarcinogens, except 4-dimethylaminoazobenzene-4'-sulfonyl chloride, were negative in mouse hepatocytes. This chemical, as well as aflatoxin G2 and pyrene, which have not been tested for carcinogenicity in the hamster, were positive in hamster hepatocytes. These findings demonstrate that genotoxic chemicals can be identified by the HPC/DNA repair assay using hamster or mouse hepatocytes. Furthermore, in vivo differences in susceptibility to chemical carcinogens such as aflatoxin B1 are reflected in the in vitro assay.