Sex-dependent promoting effect of polychlorinated biphenyls on enzyme-altered islands induced by diethylnitrosamine in rat liver.
The promoting effect of Clophen A 50, a commercial mixture of polychlorinated biphenyls (PCBs) on preneoplastic islands, initiated by diethylnitrosamine (DEN), was studied in male and female Sprague-Dawley rats. The islands were identified histochemically by loss of adenosine-5'-triphosphatase (ATPase) and/or emergence of gamma-glutamyltranspeptidase (GGTase). Treatment with 12 X 8 mg DEN/kg body wt./day initiated a similar number and total area of islands in males and females. Additional weekly application of Clophen A 50 (50 or 100 mg/kg body wt./week, for 7 weeks) enhanced the number of ATPase-deficient islands 3-fold in males and 9-fold in females. The total area was increased 4-fold in males and 15-fold in females. Number and area of GGTase-positive islands were similarly enhanced. The emergence of a small number of islands after application of Clophen A 50 alone may indicate a weak carcinogenic potency. PCB treatment caused an increase in liver weight, which amounted to approximately 55% in males and 20% in females compared to controls. This increase is partly due to cell hypertrophy, as indicated by determination of cell size. The mitogenic activity of Clophen A 50 was evaluated by measurement of the mitotic index of unaltered hepatocytes at 24, 48 h, and 7 days after application of a single dose (100/mg/kg body wt.) of Clophen A 50. The mitotic index in control animals of both sexes was approximately 0.3%, and was enhanced approximately 8-fold in males, 24 h after PCB treatment. In females only a slight, non-significant increase was observed. The results indicate that the sex-dependent promoting effect of Clophen A 50 is independent from its mitogenic action.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D008938:Mitosis / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
D009602:Nitrosamines; D004052:Diethylnitrosamine; D011078:Polychlorinated Biphenyls; D000251:Adenosine Triphosphatases