In vitro studies on non-genotoxic 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 cultures of isolated cells. The test substance was added at the start and at 24hr. At 48hr the cultures were stained with antibodies against 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-negative 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 non-carcinogens, none induced a selective inhibition of DNA synthesis in GST-P-negative hepatocytes. These findings suggest that this model system is useful when characterizing liver carcinogens and their carcinogenic mechanisms.
Stenius
U
U
Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-17177 StockholmSweden.
Ståhl
A
A
Högberg
J
J