Seitz H K, Simanowski U A, Garzon F T, Rideout J M, Peters T J, Koch A, Berger M R, Einecke H, Maiwald M
Department of Medicine, University of Heidelberg, Federal Republic of Germany.
Gastroenterology. 1990 Feb;98(2):406-13. doi: 10.1016/0016-5085(90)90832-l.
Prospective epidemiologic studies have reported an increased risk of rectal cancer following chronic ethanol ingestion. The effect of ethanol on chemically induced colorectal carcinogenesis is controversial depending on the experimental conditions. In the present study the effect of chronic ethanol administration on acetoxymethylmethylnitrosamine-induced rectal cancer and the possible role of acetaldehyde in this process were investigated. Chronic ethanol administration resulted in an earlier occurrence of rectal tumors in this animal model. Because the concomitant administration of cyanamide, a potent acetaldehyde dehydrogenase inhibitor, showed a positive trend toward increased incidences of tumors, acetaldehyde could be involved in the ethanol-associated carcinogenesis. To measure colonic acetaldehyde, 12 chronically ethanol-fed and control rats received an acute dose of ethanol (2.5 g/kg body wt). The mucosal concentration of acetaldehyde was significantly higher in the rectum compared with the cecum (198 +/- 23 vs. 120 +/- 23 nmoles.g colon-1, p less than 0.05), but was not affected by chronic ethanol feeding. Furthermore, 6 germ-free rats had significantly lower acetaldehyde concentrations in the rectum (84 +/- 11 vs. 234 +/- 33 nmoles.g colon-1, p less than 0.01) and in the cecum (59 +/- 13 vs. 121 +/- 33 nmoles.g colon-1, p less than 0.05) compared with 6 conventional animals, and this was paralleled by the number of fecal bacteria in the 2 intestinal segments. In addition, to determine the effect of chronic ethanol feeding on colorectal cell turnover, 30 animals were pair-fed liquid diets. Using the metaphase-arrest technique, alcohol feeding induced rectal (19.1 +/- 2.0 vs. 9.1 +/- 1.8 cells.crypt-1.h-1, p less than 0.01), but not cecal (18.9 +/- 1.3 vs. 22.2 +/- 3.3 cells.crypt-1.h-1, p greater than 0.05) hyperregeneration. This was accompanied by an increase in the crypt proliferative compartment and increased mucosal ornithine decarboxylase activity (63 +/- 18 vs. 22 +/- 6 pmoles.hr-1.mg protein-1, p less than 0.05). The data show that chronic ethanol ingestion accelerates chemically induced rectal carcinogenesis and raise the possibility that acetaldehyde probably generated through bacterial ethanol oxidation may be involved in this process. The secondary hyperregeneration of the mucosa, observed after alcohol feeding, could by itself favour carcinogenesis.
前瞻性流行病学研究报告称，长期摄入乙醇后直肠癌风险增加。乙醇对化学诱导的结直肠癌发生的影响因实验条件而异，存在争议。在本研究中，研究了长期给予乙醇对乙酰氧甲基甲基亚硝胺诱导的直肠癌的影响以及乙醛在此过程中的可能作用。在该动物模型中，长期给予乙醇导致直肠癌更早发生。由于同时给予强效乙醛脱氢酶抑制剂氨甲环酸显示出肿瘤发生率增加的积极趋势，因此乙醛可能参与了与乙醇相关的致癌过程。为了测量结肠中的乙醛，给12只长期喂食乙醇的大鼠和对照大鼠急性注射一剂乙醇（2.5 g/kg体重）。与盲肠相比，直肠中乙醛的黏膜浓度显著更高（198±23对120±23 nmol·g结肠-1，p<0.05），但不受长期乙醇喂养的影响。此外，与6只常规动物相比，6只无菌大鼠直肠（84±11对234±33 nmol·g结肠-1，p<0.01）和盲肠（59±13对121±33 nmol·g结肠-1，p<0.05）中的乙醛浓度显著更低，这与两个肠段中的粪便细菌数量情况相似。另外，为了确定长期乙醇喂养对结直肠细胞更新的影响，对30只动物进行配对喂食流质饮食。使用中期阻断技术，喂食乙醇会诱导直肠（19.1±2.0对9.1±1.8个细胞·隐窝-1·小时-1，p<0.01）而非盲肠（18.9±1.3对22.2±3.3个细胞·隐窝-1·小时-1，p>0.05）的超再生。这伴随着隐窝增殖区的增加以及黏膜鸟氨酸脱羧酶活性的增加（63±18对
