Ethanol Promotes Intestinal Tumorigenesis in the MIN Mouse

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

Abstract

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.

Footnotes

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↵1 These data were presented in abstract form at the 102^th Annual Meeting of the American Gastroenterological Association in Atlanta, Georgia, May 21–24, 2001.
↵2 To whom requests for reprints should be addressed. Present address: Department of Internal Medicine, Evanston-Northwestern Healthcare Research Institute, 1001 University Place, Suite 213, Evanston IL 60201. Fax: (847) 570-8011; E-mail: h-roy{at}northwestern.edu
↵3 The abbreviations used are: APC, adenomatous polyposis coli; MAA, malondialdehyde-acetaldehyde; PCNA, proliferating cell nuclear antigen.
- Accepted August 21, 1902.
- Received November 12, 1901.
- Revision received August 14, 1902.