Blanck A, Hansson T, Gustafsson J A, Eriksson L C
Carcinogenesis. 1986 Jun;7(6):981-5. doi: 10.1093/carcin/7.6.981.
We previously reported on sex differences in chemical hepatocarcinogenesis studied in the resistant hepatocyte model and on the effects of implantation of ectopic pituitary grafts into male rats on the early stages of liver carcinogenesis. Marked sex differences were found in the area ratio of enzyme-altered foci (mm2 foci/cm2 liver section) in sexually mature male and female Wistar rats (male greater than female). Pituitary grafts implanted one week before 2-acetylaminofluorene selection in male rats decreased the area ratio to a level near that of sham operated females. The present study was performed in order to investigate the relevance of the results in the short-term experiment in terms of hepatoma formation. To study the importance of 2-acetylaminofluorene selection as a determinant of the observed sex differences an experiment was also performed using the Pitot-model, where male and female rats were initiated with diethylnitrosamine and promotion was performed with phenobarbital. The long-term experiments in the resistant hepatocyte model showed that male rats develop hepatomas earlier than female rats and also showed a tendency towards a prolonged latency time in male rats bearing pituitary grafts. A good correspondence was thus achieved between the short-term and the long-term experiments. The rats treated according to the Pitot-model did not develop hepatomas within the experimental period. Of the rats killed at 13 months, three (out of five) male and five (out of five) female rats had hepatocyte nodules whereas, at 19 months two (out of six) male and five (out of six) female rats had developed such lesions in this model. We therefore conclude that 2-acetylaminofluorene is the factor responsible for the sex differences in the resistant hepatocyte model and that the hypothalamo-pituitary influence during 2-acetylaminofluorene selection is an important modifier of the carcinogenetic process.
我们之前报道了在抗性肝细胞模型中研究的化学性肝癌发生中的性别差异，以及将异位垂体移植到雄性大鼠体内对肝癌发生早期阶段的影响。在性成熟的雄性和雌性Wistar大鼠（雄性大于雌性）中，发现酶改变灶的面积比（mm²灶/ cm²肝脏切片）存在明显的性别差异。在雄性大鼠中，于2-乙酰氨基芴选择前一周植入垂体移植，可使面积比降至假手术雌性大鼠的水平附近。进行本研究是为了从肝癌形成的角度研究短期实验结果的相关性。为了研究2-乙酰氨基芴选择作为观察到的性别差异的决定因素的重要性，还使用皮托模型进行了一项实验，其中雄性和雌性大鼠用二乙基亚硝胺启动，并用地塞米松进行促癌。抗性肝细胞模型中的长期实验表明，雄性大鼠比雌性大鼠更早发生肝癌，并且在带有垂体移植的雄性大鼠中也显示出潜伏期延长的趋势。因此，短期和长期实验之间取得了良好的对应关系。按照皮托模型处理的大鼠在实验期内未发生肝癌。在13个月处死的大鼠中，五只雄性大鼠中有三只、五只雌性大鼠中有五只出现肝细胞结节，而在19个月时，六只雄性大鼠中有两只、六只雌性大鼠中有五只在该模型中出现了此类病变。因此，我们得出结论，2-乙酰氨基芴是抗性肝细胞模型中性别差异的原因，并且在2-乙酰氨基芴选择期间下丘脑-垂体的影响是致癌过程的重要调节因素。
