IN-VITRO STUDIES ON NONGENOTOXIC CARCINOGENS - RESISTANCE TO DNA-SYNTHESIS INHIBITION IN GST-P-POSITIVE HEPATOCYTES ISOLATED FROM ENZYME-ALTERED FOCI-BEARING RATS

Hepatocytes were isolated from enzyme-altered foci (EAF)-bearing rats. Carcinogen-induced effects on DNA synthesis were studied in primary c ultures of isolated cells. The test substance was added at the start a nd at 24 hr. At 48 hr the cultures were stained with antibodies agains t glutathione S-transferase P (GST-P) and DNA synthesis was estimated by thymidine incorporation. It was found that four of nine carcinogens induced a clear selective inhibition of DNA synthesis in GST-P-negati ve cells. Two of the four inhibiting carcinogens induced p53 in GST-P- negative cells, but did not in GST-P-positive cells. Of four tested no n-carcinogens, none induced a selective inhibition of DNA synthesis in GST-P-negative hepatocytes. These findings suggest that this model sy stem is useful when characterizing liver carcinogens and their carcino genic mechanisms. (C) 1998 Elsevier Science Ltd. All rights reserved.