Alkylation of porcine nucleic acids following intravenous and intragastric application of n-methyl-n-nitrosourea.

Abstract

Alkylation of nucleic acids was measured 3 h after the administration of N-(14C)-methyl-N-nitrosourea (10 mg/kg) to Hanford mini pigs. After intravenous injection the amount of 7-methylguanine formed in DNA and RNA of liver, kidney, intestines, and brain, was 2–3 times higher than after administration of a similar dose by stomach tube. In the stomach, however, the level of alkylation was more than 8 times higher after intragastric application when compared to intravenous injection. In vitro studies on the stability of N-methyl-N-nitrosourea in gastric juice indicate that no significant decomposition of the carcinogen occurred within the gastric lumen. This suggests that after application by stomach tube a substantial proportion of N-methyl-N-nitrosourea reacts with stomach cells during resorption. The results are discussed with respect to current investigations on the carcinogenic effect of N-methyl-N-nitrosourea in this species.