32P-postlabeling analysis of peroxisome proliferator-DNA adduct formation in rat liver in vivo and hepatocytes in vitro.
Hepatocarcinogenic peroxisome proliferators, clofibrate, ciprofibrate, Wy-14643 or di(2-ethylhexyl)phthalate, were administered once daily by gavage to groups of three male F344 rats for 3 days and the rats were killed 2 h after the last dose. The DNA isolated from the livers was analyzed for possible carcinogen-DNA adducts, by a most sensitive 32P-postlabeling technique which can detect one adduct in 10(10) nucleotides. No adducts were detected by this assay in the DNA isolated from the livers of rats treated with any of the peroxisome proliferators. Adducts were also not found in the DNA of hepatocytes exposed in vitro to these peroxisome proliferators for 4 h in primary suspension cultures. Failure to detect peroxisome proliferator DNA adducts in hepatocytes under in vivo and in vitro conditions supports the contention that formation of a peroxisome proliferator-DNA adduct is not an essential step in the carcinogenesis by this novel class of carcinogens.
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002273:Carcinogens; D002994:Clofibrate / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004247:DNA; D004051:Diethylhexyl Phthalate / Q000494:pharmacology; D058607:Fibric Acids; D000960:Hypolipidemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D010761:Phosphorus Radioisotopes; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats
D000924:Anticholesteremic Agents; D002273:Carcinogens; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D010761:Phosphorus Radioisotopes; D011743:Pyrimidines; D002995:Clofibric Acid; C006253:pirinixic acid; D004247:DNA; D004051:Diethylhexyl Phthalate; C019304:ciprofibrate; D002994:Clofibrate