Sex-dependent promoting effect of polychlorinated biphenyls on enzyme-altered islands induced by diethylnitrosamine in rat liver

Abstract

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.

Effects of PCBs and related compounds on hepatocarcinogenesis in rats and mice.

“…By comparing the number of enzymealtered foci resulting from administration of the initiator alone with the number and area of foci resulting from administration of the initiator and then the suspected promoter, one can obtain an assessment of the tumor promoting effects of chemicals such as PCBs. By using such procedures, Deml and Oesterle (18) found that Clophen A 50, a commercial mixture of PCBs, had greater promoting effects in livers from female rats when compared to the effects in males. They also reported that weanling rats were much more susceptible to the promoting effects of PCBs than adult rats (19).…”

Polychlorinated Biphenyls and Polybrominated Biphenyls

“…The promoting activity of PCBs was observed in males and females. In one study, the promoting activity 380 of Clophen A 50 was much higher in female rats than in males (Deml & Oesterle, 1982); a similar observation was made for phenobarbital (Xu et al, 1990). In mice, males are more susceptible than females to hepatocarcinogenesis; higher production of IL-6 by Kupffer cells in males may be responsible for this sex-specific difference (Naugler et al, 2007).…”

Carcinogenicity of Black Rock Harbor Sediment to the Eastern Oyster and Trophic Transfer of Black Rock Harbor Carcinogens from the Blue Mussel to the Winter Flounder

“…At sufficient concentrations, these might act as complete carcinogens; at lower concentrations, they may be more important as initiators. Other compounds (e.g., chlordanes, DDTs, and PCBs) found in the tumorigenic sediment may be more important as promoters (43)(44)(45).…”