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Deml, E. ; Oesterle, D.

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

Carcinogenesis 3, 1449-1452 (1982)

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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 ~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, 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 ~0.3%, and was enhanced 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.

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