title: Ethanol promotes intestinal tumorigenesis in the MIN mouse. Multiple intestinal neoplasia.
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.
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center and Omaha Veterans Administration Medical Center, Omaha, Nebraska, USA. h-roy@northwestern.edu
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Roy
authors.forename: James M
authors.initials: JM
authors.lastname: Gulizia
authors.forename: William J
authors.initials: WJ
authors.lastname: Karolski
authors.forename: Anne
authors.initials: A
authors.lastname: Ratashak
authors.forename: Michael F
authors.initials: MF
authors.lastname: Sorrell
authors.forename: Dean
authors.initials: D
authors.lastname: Tuma
mesh_terms: D000015:Abnormalities, Multiple / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D000079:Acetaldehyde / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004253:DNA Nucleotidylexotransferase / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000187:drug effects; D012377:Rodentia / Q000276:immunology / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D000431:Ethanol; D008315:Malondialdehyde; D004253:DNA Nucleotidylexotransferase; D000079:Acetaldehyde