This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roy, H. K. Articles by Tuma, D. Search for Related Content PubMed PubMed Citation Articles by Roy, H. K. Articles by Tuma, D.

Ethanol Promotes Intestinal Tumorigenesis in the MIN Mouse¹

Departments of Internal Medicine [H. K. R., W. J. K., A. R., M. F. S., D. T.] and Pathology and Microbiology [J. M. G.], University of Nebraska Medical Center and Omaha Veterans Administration Medical Center, Omaha, Nebraska

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.

This article has been cited by other articles:

				J. Pannequin, N. Delaunay, C. Darido, T. Maurice, P. Crespy, M. A. Frohman, M. S. Balda, K. Matter, D. Joubert, J.-F. Bourgaux, et al. Phosphatidylethanol Accumulation Promotes Intestinal Hyperplasia by Inducing ZONAB-Mediated Cell Density Increase in Response to Chronic Ethanol Exposure Mol. Cancer Res., November 1, 2007; 5(11): 1147 - 1157. [Abstract] [Full Text] [PDF]

				A. L. Zisman, A. Nickolov, R. E. Brand, A. Gorchow, and H. K. Roy Associations between the age at diagnosis and location of colorectal cancer and the use of alcohol and tobacco: implications for screening. Arch Intern Med, March 27, 2006; 166(6): 629 - 634. [Abstract] [Full Text] [PDF]

				P. Watson, R. Ashwathnarayan, H. T. Lynch, and H. K. Roy Tobacco Use and Increased Colorectal Cancer Risk in Patients With Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) Arch Intern Med, December 13, 2004; 164(22): 2429 - 2431. [Abstract] [Full Text] [PDF]