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United States Department of Agriculture

Agricultural Research Service

Title: Enhancement of Ethanol-Induced Rectal Mucosal Hyperregeneration with Age in F344 Rats

Authors
item Simanowski U A, - HEIDELBERG UNIV
item Suter P, - UNIV HOSP, ZURICH
item Russell R M, - TUFTS-HNRCA
item Heller M, - HEIDELBERG UNIV
item Waldherr R, - HEIDELBERG UNIV
item Ward R, - KINGS COLLEGE
item Peters T J, - KINGS COLLEGE
item Smith D, - TUFTS-HNRCA
item Seitz H K, - HEIDELBERG UNIV

Submitted to: Gut
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 8, 1993
Publication Date: N/A

Interpretive Summary: Increased cell reproduction is thought to be a precursor to the development of cancer. Studies in rats have shown that rectal cell turnover is increased with age and moreover, that cell turnover can be stimulated by chronic alcohol consumption. In the present study, young and old rats were fed 36% of total calories per day either as ethanol or as substituted carbohydrates. Age did not affect either colon or rectal- cell reproduction. However, alcohol consumption did stimulate rectal but not colon-cell reproduction. A toxic breakdown product of ethanol (acetaldehyde) was measured in tissue, and there was found to be a correlation in rectal tissue between acetaldehyde concentrations and cell reproduction. This may, in part, explain higher rectal cancer rates in alcoholic people and suggests a mechanism whereby alcohol drinking could favor the development of such cancer.

Technical Abstract: Experimental studies in rats have shown an independent stimulation of rectal cell turnover by either chronic ethanol consumption or age. We investigated the combined effect of these two factors on colorectal cell regeneration. Ninety male F344 aged 1, 12, and 22 mos were pair-fed nutritionally adequate liquid diets containing 36% of total energy either as ethanol or isoenergetic carbohydrates. After four wks, colorectal crypt cell production rates were measured using a stathmokinetic technique with vincristine. While age alone did not affect colorectal cell renewal, chronic ethanol consumption stimulated rectal, but not colonic crypt cell production rate in an age dependent manner. While no significant effect of ethanol was noted in young animals, cell proliferation was signifi- cantly enhanced in middle-aged animals by 81% (4.1 (2.7-5.5) vs. 7.4 (6.0-8.7) cells/crypt/hour, p<0.001) after ethanol ingestion. Because acetaldehyde, the first and most toxic metabolite of ethanol has been detected in the colorectal mucosa and may lead to tissue injury in- fluencing cell regeneration, acetaldehyde concentrations have been measured in the colons of 15 male F344 rats of various ages after an acute intraperitoneal dose of ethanol (2.5 g/kg body weight). There was significant positive correlation between crypt cell production rate and acetaldehyde concentrations measured in the distal and proximal colon after an acute dose of ethanol (r=0.5955, p<0.005, p<0.005). These data show that the ethanol-mediated stimulation of cell regeneration in the rectum is age-dependent. We found indirect evidence that acetaldehyde participates in the pathogenesis of rectal hyperregeneration after chronic alcohol consumption which could be itself favor carcinogenesis.

Last Modified: 10/23/2014
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