Methylation of DNA in stomach and small intestine of rats after oral administration of methylamine and nitrite

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Abstract
Young adult male Sprague-Dawley rats were given 30 .mu.mol/kg body wt [14C]methylamine hydrochloride and 700 .mu.mol/kg body wt sodium nitrite by oral gavage. DNA isolated from the stomach and from the first 15 cm of the small intestine was methylated, containing 7-methylguanine (7mG) at a level of one 7mG molecule/5x 106 and 1x 107 nucleotides, respectively. No 7mG was found in the liver at a limit of detection of one 7mG molecule/2x 108 nucleotides. In a 2nd experiment, the excised stomachs were incubated with DNase before the isolation of the DNA in order to degrade DNA in the lumen and in the uppermost lining cells. This treatment resulted in a 30% decrease in the yield of DNA and a 90% reduction in the level of 7mG formation. Thus, nitrosation of a primary alkylamine yields a precursor of an alkylating agent which has a long enough lifetime to diffuse towards and react with intracellular DNA. A correlation of DNA methylation in the stomach with the corresponding tumor formation by the methylating carcinogen N-methyl-N''-nitro-N-nitrosoguanidine was used to estimate the role of DNA damage resulting from endogenous nitrosation of dietary methylamine in man. The risk resulting from this single amine must be negligible but a similar evaluation of other primary amines is required before the overall role of primary amine nitrosation in the etiology of human gastric cancer can be assessed.