Stewart F P, Manson M M, Cabral J R, Smith A G
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, UK.
Carcinogenesis. 1989 Jul;10(7):1225-30. doi: 10.1093/carcin/10.7.1225.
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.
在大鼠中，六氯苯（HCB）主要在雌性大鼠中引发尿卟啉症和肝肿瘤。为了研究HCB的促癌特性，雄性和雌性大鼠饮用含0.015%二乙基亚硝胺（DEN）的水3周。在2周的恢复期后，大鼠被喂食对照饮食或含0.02%HCB的饮食30周。从可见肿瘤的大小和数量以及γ-谷氨酰转肽酶（GGT）活性染色呈强阳性的肝切片百分比判断，HCB是DEN引发的两性肝癌发生的有效促癌剂。雄性大鼠的肿瘤更大，而雌性大鼠中GGT阳性肿瘤和非肿瘤组织的区域更大。仅在接受HCB或DEN/HCB处理的雌性大鼠肝脏中发生血红素生物合成酶尿卟啉原脱羧酶（UD）的抑制。在后一组中，UD在肿瘤内和肿瘤外均受到抑制，而尿卟啉仅在非癌组织中积累。在雄性大鼠肝脏中未观察到UD的显著抑制。在另一项研究中，大鼠腹腔注射一剂DEN（20mg/kg），3周后喂食HCB 30周。HCB使两性中GGT阳性病灶的数量大幅增加，但在雄性中尤为明显（比雌性高1.4倍）。因此，HCB被证明是肝癌发生过程中的促癌剂。然而，缺乏一致的明显性别差异表明，对于单独长期施用这种化学物质时主要在雌性中发生的肿瘤诱导，这只是部分解释。
