Sex and strain differences in the hepatocyte primary culture/DNA repair test

The hepatocyte primary culture (HPC)/DNA repair test was developed using hepatocytes isolated from male F-344 rats. A number of genetic polymorphisms have been shown to occur in inbred strains of rats, which may lead to variation in biotransformation of xenobiotics resulting in differences in susceptibility to genotoxins. The effect of the strain utilized as a source of hepatocytes was investigated with female Lewis, F-344, and DA rats. Variation was observed when hepatocytes from the three strains were exposed to aflatoxin B1 (AFB1). Hepatocytes from female Lewis rats were more sensitive to AFB1 genotoxicity than cells from F-344 or DA rats. DNA repair was induced by a concentration as low as 10(-8) M AFB1 in the Lewis strain while 10(-4) M was needed for hepatocytes from female F-344 or DA rats. Sex-related differences were also observed with AFB1; DNA repair was induced at 10(-8) M in hepatocytes from male F-344 rats. No clearcut strain differences were seen when cells were exposed to diethylnitrosamine (DEN) or 2-acetylaminofluorene, although 10(-2) M DEN was only cytotoxic to hepatocytes from DA rats. These results demonstrate that both the strain and the sex of the animal used as a source of hepatocytes can affect the HPC/DNA repair test.