Hepatocarcinogenicity of hexachlorobenzene in rats and the sex difference in hepatic iron status and development of porphyria

摘要: Hexachlorobenzene (HCB) was fed to male and female F344 rats as 0.02% of the diet for 15 weeks. Females developed a massive porphyria, due depression uroporphyrinogen decarboxylase activity, whereas males did not. Although hepatic non-haem iron levels in control females were 3-5 times greater than (iron is implicated pathogenesis this condition) preloading latter with not increase their susceptibility. After 90 weeks HCB treatment 100% surviving had multiple liver tumours which strongly gamma-glutamyl transpeptidase (GGT) positive histologically classified neoplastic nodules or hepatocellular carcinomas. In contrast, only 16% smaller fewer number per those females. Accumulation porphyrins still significantly less although no activity detected treated livers either sex. No differences porphyrin enzyme found between surrounding tissue showing that revert non-porphyric state. The sex difference tumour response could be explained by concentrations. Non-haem concentrations fell after both sexes even lower tumours. These studies demonstrate are far more sensitive porphyrinogenic effects but also hepatocarcinogenic actions, suggesting link these two manifestations toxicity may apply other polyhalogenated aromatics.