| 2736716 |
Stewart FP, Manson MM, Cabral JR, Smith AG: Hexachlorobenzene as a promoter of diethylnitrosamine-initiated hepatocarcinogenesis in rats and comparison with induction of porphyria. Carcinogenesis. 1989 Jul;10(7):1225-30.
In rats, hexachlorobenzene (HCB) causes uroporphyria and liver tumours predominantly in females. To investigate the promotional properties of HCB, male and female rats received diethylnitrosamine (DEN) in the drinking water (0.015%) for 3 weeks. After a 2-week recovery period rats were fed control diet or one containing HCB (0.02%) for 30 weeks. HCB was an efficient promoter of DEN-initiated hepatocarcinogenesis in both sexes as judged by the size and numbers of visible tumours and by the percentage of liver sections that stained strongly positive for gamma-glutamyltranspeptidase (GGT) activity. Tumours were larger in males whereas regions of GGT-positive tumour and non-tumour tissue were greater in females. Inhibition of the haem biosynthesis enzyme uroporphyrinogen decarboxylase (UD) only occurred in the liver of females treated with HCB or DEN/HCB. In the latter group, UD was inhibited both in and outside tumours whereas uroporphyrin only accumulated in non-cancerous tissue. No significant inhibition of UD was observed in the liver of males. In another study, rats received one i.p. dose of DEN (20 mg/kg) and after 3 weeks were fed HCB for 30 weeks. Numbers of GGT-positive foci were greatly increased by HCB in both sexes, but especially in males (1.4-fold greater than females). Thus HCB was shown to be a promoter of hepatocarcinogenesis. However, the lack of a consistent marked sex difference suggests that this is only a partial explanation for the induction of tumours which mainly occur in females when this chemical is administered alone for prolonged periods. |
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