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

流行病学研究证实，重度饮酒者患食道癌的频率较高。然而，导致这种高频率的机制细节尚未得到澄清。亚硝胺是一种致癌物，人类一生都会接触到亚硝胺。n -亚硝基甲基苄胺（NMBA）是一种亚硝胺，可导致食道癌。近年来，细胞色素P4502E1 （CYP2E1）被乙醇诱导并代谢NMBA的研究已经明确。乙醇对CYP2E1的诱导不仅发生在食道，也发生在肝脏等器官。在本研究中，我们分析了乙醇对NMBA治疗大鼠食管癌发展的影响。方法：Wister雄性大鼠20只，根据所喂液体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%），对照组与对照饲料（等热量用碳水化合物代替乙醇）配对喂养2周。初饲后，每周2次腹腔注射0.1 mg/kg体重/天的NMBA，配合流质日粮，连续10周。治疗30周后，处死大鼠。结果：乙醇处理大鼠食管可见乳头状瘤5 ~ 8个，对照组10只大鼠中5只可见1个。在乙醇处理的大鼠食管上皮中，CYP2E1染色强烈，而在对照大鼠中没有染色。结论：提示酒精可促进大鼠食管癌的发生发展。

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.