Roy Hemant K, Gulizia James M, Karolski William J, Ratashak Anne, Sorrell Michael F, Tuma Dean
Department of Internal Medicine, University of Nebraska Medical Center and Omaha Veterans Administration Medical Center, Omaha, Nebraska, USA.
Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1499-502.
Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer; however, these data are confounded by numerous cosegregating variables. Previous experimental reports with the rodent carcinogen model have also yielded discordant results. To clarify the alcohol-colon cancer relationship, we used the MIN (multiple intestinal neoplasia) mouse, a genetic model of intestinal tumorigenesis. Twenty-four MIN mice were randomized to ethanol supplementation in the drinking water (15% alternating with 20% on a daily basis) or control. Mice were sacrificed after 10 weeks, and the intestinal tumors were scored under magnification. Tissue sections were assessed for apoptosis and cell proliferation rates, along with the presence of the malondialdehyde-acetaldehyde (MAA) adduct, a mutagenic adduct associated with ethanol consumption. Ethanol supplementation resulted in a significant increase in tumor number (135 +/- 35%; P = 0.027 versus control). The induction of tumorigenesis by ethanol was most dramatic in the distal small bowel (167 +/- 56%; P = 0.01). In the uninvolved intestinal mucosa, there was no difference in proliferative or apoptotic indices. Cytoplasmic and nuclear MAA adducts were detected in both ethanol-treated and control mice. We demonstrated that ethanol ingestion increased intestinal tumorigenesis in the MIN mouse model. Furthermore, whereas mechanisms remain incompletely elucidated, our data implicate formation of MAA adducts. This report provides further support that ethanol consumption is a risk factor for colorectal cancer.
流行病学研究表明，饮酒会增加患结直肠癌的风险；然而，这些数据受到众多共同存在的变量的干扰。以往关于啮齿动物致癌物模型的实验报告也得出了不一致的结果。为了阐明酒精与结肠癌的关系，我们使用了MIN（多重肠道肿瘤）小鼠，这是一种肠道肿瘤发生的遗传模型。将24只MIN小鼠随机分为饮用水中添加乙醇组（每天15%与20%交替）或对照组。10周后处死小鼠，在显微镜下对肠道肿瘤进行评分。对组织切片进行凋亡和细胞增殖率评估，同时检测丙二醛-乙醛（MAA）加合物的存在情况，该加合物是一种与饮酒相关的诱变加合物。补充乙醇导致肿瘤数量显著增加（135±35%；与对照组相比，P = 0.027）。乙醇诱导的肿瘤发生在远端小肠最为显著（167±56%；P = 0.01）。在未受累的肠黏膜中，增殖或凋亡指数没有差异。在乙醇处理组和对照组小鼠中均检测到细胞质和细胞核MAA加合物。我们证明，在MIN小鼠模型中，摄入乙醇会增加肠道肿瘤发生。此外，虽然机制仍未完全阐明，但我们的数据表明MAA加合物的形成与之有关。本报告进一步支持饮酒是结直肠癌的一个风险因素。
