Fas-mediated apoptosis is attenuated in preneoplastic GST-P-positive hepatocytes isolated from diethylnitrosamine-treated rats.
Previous reports have indicated that apoptosis is selectively decreased in enzyme-altered foci (EAF) in the livers of rats treated with a carcinogen. Here we have investigated the effects of an anti-Fas antibody (anti-Fas Ab) on EAF cells in vitro. Hepatocytes were isolated from rats treated repeatedly with diethylnitrosamine (DEN), whose livers contained glutathione S-transferase P (GST-P)-positive EAF. Subsequently, primary cultures of GST-P-positive and GST-P-negative hepatocytes were established and exposed to anti-Fas Ab. Anti-Fas Ab (4 microg/ml) preferentially induced apoptosis in GST-P-negative cells. Furthermore, GST-P-positive cells were shown to be resistant to p53-mediated apoptosis. We conclude that EAF hepatocytes are resistant to Fas-mediated apoptosis in vitro. This lack of response may explain the selective decrease in apoptosis in EAF.
Nordstrand
M
M
Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
Stenius
U
U
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis; D002273:Carcinogens / Q000633:toxicity; D002478:Cells, Cultured; D004052:Diethylnitrosamine / Q000633:toxicity*; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides; D019014:fas Receptor / Q000502:physiology*
D000906:Antibodies; D014408:Biomarkers, Tumor; D002273:Carcinogens; D020319:Oligodeoxyribonucleotides, Antisense; D013873:Thionucleotides; D019014:fas Receptor; D004052:Diethylnitrosamine; D005982:Glutathione Transferase