Methylation of intestinal and hepatic DNA in rats treated with methylazoxymethanol acetate.

Descending colon is the most sensitive segment of rat intestine and is at least as sensitive as liver to the carcinogenic effects of methylazoxymethanol acetate. To determine whether a relationship exists between tumor induction and level of DNA methylation, we measured the levels of 7-methylguanine in the DNA isolated from duodenum, descending colon, and liver of rats treated with this carcinogen. Because radiolabeled methylazoxymethanol acetate is not available, we utilized high pressure liquid chromatography whereby methylated purines could be detected in amounts as little as 100-300 pmoles. DNA isolated from liver of carcinogen-treated rats had significant amounts of 7-methylguanine. On the contrary, DNA isolated from descending colon of rats treated with methylazoxymethanol acetate had minimal amounts of 7-methylguanine; these data suggest that the level of 7-methylguanine does not correlate with sensitivity to tumor induction by methylazoxymethanol acetate.