Effect of long-term ethanol consumption on the development of gastrointestinal cancer.

流行病学研究证实，大量饮酒的人患食道癌的频率很高。然而，导致这种高频率的机制的细节还没有弄清楚。人类在一生中暴露在亚硝胺中，亚硝胺是一种致癌物。N-亚硝基甲基苄胺(NMBA)是一种亚硝胺，可导致食道癌。近年来发现，细胞色素P4502E1(CYP2E1)在乙醇诱导下代谢NMBA。乙醇对细胞色素P4502E1的诱导作用发生在食道、肝脏等器官。方法：Wistar雄性大鼠20只，按饲喂流质饲料的不同分为乙醇组和对照组。乙醇组给予含乙醇的液体饲料(占总热量的36%)，对照组给予对照饲料，用碳水化合物等热量替代乙醇，持续2周。灌胃给药后，NMBA 0.1 mg/kg体重/d，每周2次，连续10周。治疗30周后处死大鼠。结果：所有酒精处理组大鼠食管内可见5~8个乳头状瘤，而对照组10只大鼠中只发现5个。在乙醇处理组大鼠的食道上皮细胞中，细胞色素P450-2E_1呈强阳性表达，而对照组大鼠未见表达。结论：酒精对大鼠食道癌的发生有促进作用。

A high frequency of esophageal cancer of heavy drinkers has been confirmed from epidemiological studies. However, details of the mechanisms causing this high frequency have not yet been clarified. Human beings are exposed nitrosamines, which is a procarcinogen, during their lifetime. N-nitrosmethylbenzylamine (NMBA), one of nitrosamines, causes esophageal cancer. Recently, it has become clear that cytochrome P4502E1 (CYP2E1) is induced by ethanol and metabolizes NMBA.The induction of CYP2E1 by ethanol is occurred in esophagus as well as liver and other organs. In this study, we analyzed the effect of ethanol on the development of esophageal cancer in rats treated with NMBA.Methods : Twenty Wister male rats were divided into two groups (ethanol and control) according to the liquid diets they were fed. Ethanol group was given an ethanol-containing liquid diet (36% of total calories), and control group was pair-fed with a control diet where ethanol was replaced isocalorically with carbohydrate for 2 weeks. After preliminary feeding, 0.1 mg/kg body weigh/day of NMBA was administered intraperitoneally twice a week for 10 weeks with liquid diets. After 30 weeks treatment, rats were killed. Results : Five to eight visible papillomas were found in esophagus of all ethanol treated rats, while only one papilloma was found five of the ten control rats. In esophageal epithelium in ethanol treated rats, CYP2E1 was stained strongly, but it was not stained in control rats. Conclusions : These results suggest that alcohol may promote the development of esophageal cancer in rats.