EFFECTS OF DIET AND ETHANOL ON THE EXPRESSION AND LOCALIZATION OF CYTOCHROMES P450 2E1 AND P450 2C7 IN THE COLON OF MALE-RATS

Local activation of procarcinogens in target tissues such as the colon by cytochrome P450-dependent microsomal monooxygenases is considered to be an important factor in the etiology of cancer. Diet and alcohol consumption are considered risk factors in colon cancer, and the cytoc hrome P450 isozymes CYP2E1 and CYP2C7 have been implicated in the bioc hemical mechanisms underlying colon cancer. The current study was cond ucted to determine the effects of diet and ethanol consumption on colo nic and hepatic expression of these two enzymes. Adult male rat Spragu e-Dawley rats were fed rat chow ad lib. or were infused intragastrical ly with control or ethanol-containing diets. Our results indicate that CYP2E1 is present in colonic epithelial cells, and expression of colo nic and hepatic microsomal CYP2E1 and CYP2C7 was increased by chronic ethanol intake. As compared with rats having ad lib. access to standar d rat: food, rats receiving total enteral nutrition had significant (P < 0.01) reductions of CYP2C7 and slight, but not statistically signif icant, reductions in the expression of CYP2E1 in colon. Diet and ethan ol differentially regulated CYPZE1 and CYP2C7 in a tissue-specific man ner such that ethanol induced CYPZE1 and CYP2C7 in the colon and liver , and the intragastric diet alone had a tendency to induce these isozy mes in the liver and reduce them in the colon. These results may provi de a partial explanation for the mechanisms underlying effects of diet and ethanol on colon cancer.