In the preceding paper (Magee & Hultin, 1962) it was shown that methylation of proteins of ratliver slices occurred during incubation of the slices with the hepatotoxin and carcinogen dimethylnitrosamine. This finding supports the hypothesis that dimethylnitrosamine undergoes enzymic oxidative N-demethylation in the liver with subsequent intracellular fornation of a methylating agent, possibly diazomethane. Evidence for reaction with nucleic acids was also obtained. The reactions of nucleic acids and their components with alkylating agents have been studied very extensively in vitro
S-Adenosylmethionine was found to methylate DNA non-enzymatically to produce the same putative promutagenic and procarcinogenic lesions formed by carcinogenic chemical methylating agents. The formation of 7-methylguanine was confirmed by u.v. spectrophotometry, the formation of O6-methylguanine and 3-methyladenine was suggested by the cochromatography of radioactivity with standard bases. It is possible that this reaction may explain the presence of constitutive cellular enzymes specifically for the repair of methylated DNA, and may indicate the mechanism whereby methylated guanine is formed in the liver DNA of rats with chemically induced liver damage.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.