Castonguay A, Rivenson A, Trushin N, Reinhardt J, Spathopoulos S, Weiss C J, Reiss B, Hecht S S
Cancer Res. 1984 Jun;44(6):2285-90.
The effects of chronic ethanol consumption on the carcinogenicity and metabolism of N'-nitrosonornicotine (NNN) in male F344 rats have been investigated. Groups of 26 to 30 rats were maintained on either a control liquid diet (Groups 1, 3, and 5) or an ethanol-containing liquid diet (Groups 2, 4, and 6) for 4 weeks prior to and during treatment with NNN. The carcinogen was injected s.c. (10 mg/kg, Groups 3 and 4) three times weekly or added to the liquid diet (17.5 mg/liter, Groups 5 and 6). The total dose was 1 mmol of NNN per rat. Control rats (Groups 1 and 2) received s.c. injections of 0.9% NaCl solution. The nasal mucosa was the main target tissue of NNN in Groups 3 and 4, but both the nasal mucosa and esophagus were major target tissues in Groups 5 and 6. In rats treated s.c. with NNN (Groups 3 and 4), ethanol consumption had no effect on the distribution and incidence of nasal cavity tumors. In rats treated with NNN added to the control liquid diet or to the ethanol-containing liquid diet, the number of tumors of the nasal cavity was 18 in Group 5 and 26 in Group 6 (p less than 0.05). In contrast, the number of rats with esophageal tumors was 25 in Group 5 and 20 in Group 6 (p less than 0.05). The effects of ethanol on the enzyme system which activates NNN were studied in rats which had been maintained on an ethanol-containing liquid diet for 4 weeks. Explants of nasal mucosae, lingual mucosae, esophagi , and livers were cultured in vitro with NNN. Nasal mucosae of ethanol-consuming rats had a 1.5-fold higher (p less than 0.05) alpha-carbon-hydroxylating activity than did those of control rats. Activating enzymes in the lingual mucosae, esophagi , and livers were not induced by ethanol. The results show that the increased susceptibility of the rat nasal mucosa to the carcinogenic effects of NNN added to an ethanol-containing diet could be due in part to an induction of activating enzymes by ethanol. However, since chronic ethanol consumption had no apparent effect on the incidence of nasal cavity tumors in rats treated by s.c. injection of NNN, factors other than enzyme induction are important in determining the effects of ethanol on NNN carcinogenicity.
研究了长期摄入乙醇对雄性F344大鼠中N'-亚硝基降烟碱（NNN）致癌性和代谢的影响。在NNN处理前及处理期间，将26至30只大鼠分为几组，分别给予对照液体饲料（第1、3和5组）或含乙醇液体饲料（第2、4和6组），持续4周。致癌物通过皮下注射（10 mg/kg，第3和4组），每周3次，或添加到液体饲料中（17.5 mg/升，第5和6组）。每只大鼠的NNN总剂量为1 mmol。对照大鼠（第1和2组）接受皮下注射0.9%氯化钠溶液。在第3和4组中，鼻黏膜是NNN的主要靶组织，但在第5和6组中，鼻黏膜和食管都是主要靶组织。在皮下注射NNN的大鼠（第3和4组）中，乙醇摄入对鼻腔肿瘤的分布和发生率没有影响。在对照液体饲料或含乙醇液体饲料中添加NNN处理的大鼠中，第5组鼻腔肿瘤数量为18个，第6组为26个（p<0.05）。相比之下，第5组食管肿瘤大鼠数量为25只，第6组为20只（p<0.05）。在持续4周给予含乙醇液体饲料的大鼠中，研究了乙醇对激活NNN的酶系统的影响。将鼻黏膜、舌黏膜、食管和肝脏的外植体与NNN一起进行体外培养。摄入乙醇的大鼠的鼻黏膜α-碳羟化活性比对照大鼠高1.5倍（p<0.05）。舌黏膜、食管和肝脏中的激活酶未被乙醇诱导。结果表明，大鼠鼻黏膜对添加到含乙醇饲料中的NNN致癌作用敏感性增加，部分原因可能是乙醇诱导了激活酶。然而，由于长期摄入乙醇对皮下注射NNN处理的大鼠鼻腔肿瘤发生率没有明显影响，除酶诱导外的其他因素在确定乙醇对NNN致癌性的影响中很重要。
