Effects of Low‐to‐Moderate Ethanol Consumption on Colonic Cell Proliferation, Differentiation and Apoptosis in Young Adult and Middle‐Aged Rats

Abstract

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk for developing colorectal cancer while others suggest that moderate alcohol consumption may provide a protective effect that reduces colorectal cancer risk. Prior experimental data have indicated the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. Chemopreventative agents are reported to decrease cell proliferation and to increase differentiation and apoptosis. The present study examined whether chronic low‐to‐moderate ethanol consumption had an effect on these parameters of colonic cell growth. Twenty‐four nondeprived young adult (109 days old) Wistar rats (n=12/group) and twenty‐four nondeprived middle‐aged (420 days old) Wistar rats (n=12/group) were allowed to voluntarily consume a 20% v/v ethanol solution on alternate days for 13 weeks (45 ethanol drinking sessions total) or were given access only to water (non ethanol‐exposed control). The intermittent access 20% ethanol drinking paradigm utilized results in mean blood alcohol levels of ~30–50 mg/dl in the outbred Wistar strain when measured 30–120 min into a standard drinking session. Following the final experimental session, colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki‐67, goblet cell and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling), respectively. Ethanol treatment resulted in a lower cell proliferation index in both young (P = 0.05) and older (P < 0.001) rats, as well as a lower proliferative zone (P < 0.01 for both ages). Older rats had a shorter colon, but there was no significant difference for proliferation index between young and old rats. Cell differentiation between ethanol‐treated animals and controls was not significant for young rats, but older rats had a lower level of differentiation in the ethanol group. For apoptosis, there was no significant effect of ethanol treatment for either young or old rats. Younger rats had higher values than older rats for both differentiation and apoptosis (P < 0.05). These findings suggest that moderate consumption of ethanol improves at least one notable parameter (cell proliferation) in colonic tumorigenesis regardless of age, however, reduced cell differentiation among older animals.Support or Funding InformationSupport Contributed By: NIH AA023291