ENHANCEMENT OF ETHANOL-INDUCED RECTAL MUCOSAL HYPER REGENERATION WITHAGE IN F344 RATS

Experimental studies in rats have shown an independent stimulation of rectal cell turnover by either chronic ethanol consumption or age. In this study the combined effect of these two factors on colorectal cell regeneration has been investigated. Ninety male F344 rats aged 2, 12, and 22 months were pair fed nutritionally adequate liquid diets conta ining 36% of total energy either as ethanol or isoenergetic carbohydra tes. After four weeks of feeding, colorectal crypt cell production rat es were measured using a stathmokinetic technique with vincristine. Wh ile age by itself did not affect colorectal cell renewal, chronic etha nol consumption stimulated rectal, but not colonic crypt cell producti on rate in an age dependent manner. While no significant effect of eth anol was noted in young animals, cell proliferation was significantly enhanced in middle aged animals by 81% (4.1 (2.7-5.5) v 7.4 (6,0-8.7) cells/crypt/hour, p<0.001) and in old animals by 138% (4.5 (3.3-5.6) v 10.7 (8.9-12.4) cells/crypt/hour, p<0.001) after ethanol ingestion. B ecause acetaldehyde, the first and most toxic metabolite of ethanol, h as been detected in the colorectal mucosa and may lead to tissue injur y influencing 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 bodyweight). There was a significant positive correlation between crypt cell production rate and acetaldehyde concentrations measured in the distal and proximal c olon after an acute dose of ethanol (r=0.5955, p<0.005). These data cl early show that the ethanol mediated stimulation of cell regeneration in the rectum is age dependent. As reported earlier, there was found i ndirect evidence that acetaldehyde participates in the pathogenesis of rectal hyperregeneration after chronic alcohol consumption. This hype rregeneration of the rectal mucosa after alcohol drinking could by its elf favour carcinogenesis, which is especially relevant in old age.