EFFECTS OF CALORIC RESTRICTION AND DIETARY-FAT ON EPITHELIAL-CELL PROLIFERATION IN RAT COLON

Epidemiological studies indicate that caloric intake and dietary fat c ontent influence colonic carcinogenesis. In rodents, caloric restricti on reduces, and some fats increase, carcinogen-induced colon cancer in cidence. The present study was designed to investigate the effects of caloric restriction on colonic cell proliferation (CCP) in carcinogen- treated or control rats fed low- or high-fat diets. F344 rats were tre ated with azoxymethane (15 mg/kg X2) and then fed an isocaloric AIN 76 A diet containing either 5 or 23% corn oil, ad libitum or calorie-rest ricted to 70 or 80% of the kilocalories consumed by ad libitum rats. B iopsies of the distal colon were taken at 10 and 20 weeks, and rats we re sacrificed at 21 or 34 weeks on the experimental diets. Distal CCP was determined by microautoradiography after [H-3]thymidine labeling i n vitro or presacrifice administration in vivo. The labeling index and number or labeled cells per crypt column were significantly reduced b y caloric restriction at all time points (10, 20, 21, 34 weeks). Calor ic restriction reduced CCP in high fat- and low fat-fed rats and in az oxymethane-treated and control rats. High fat resulted in decreased CC P in the distal colon compared to low fat al 34 weeks but not earlier. The findings indicate that: (a) caloric restriction is effective in f avorably modulating CCP, an intermediate biomarker of colon cancer ris k; (b) a high fat ad libitum diet, which increased tumor yield, does n ot increase distal colon proliferation, (c) dietary fat intake alters proliferation in a manner differing from that induced by changing diet ary caloric intake.