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 ofpolychlorinated biphenyis (PCBs) on preneoplastic islands, initiatedby diethylnitrosamine (DEN), was studied in male and femaleSprague-Dawley rats. The islands were identified histochemicallyby loss of adenosine-5'-triphosphatase (ATPase) and/or emergenceof gamma-glutamyltranspeptidase (GGTase). Treatment with 12x 8 mg DEN/kg body wt./day initiated a similar number and totalarea of islands in males and females. Additional weekly applicationof Clophen A 50 (50 or 100 mg/kg body week, for 7 weeks) enhancedthe number of ATPase-deficient islands 3-fold in males and 9-foldin females. The total area was increased 4-fold in males and15-fold in females. Number and area of GGTasepositive islandswere similarly enhanced. The emergence of a small number ofislands after application of Clophen A 50 alone may indicatea weak carcinogenic potency. PCB treatment caused an increasein liver weight, which amounted to 55% in males and 20% in femalescompared to controls. This increase is partly due to cell hypertrophy,as indicated by determination of cell size. The mitogenic activityof Clophen A 50 was evaluated by measurement of the mitoticindex of unaltered hepatocytes at 24, 48 h, and 7 days afterapplication of a single dose (100/mg/kg body wt.) of ClophenA 50. The mitotic index in control animals of both sexes was0.3%, 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 effectof Clophen A 50 is independent from its mitogenic action.