Comparative Studies of the Hepatocarcinogen N,N-Dimethylnitrosamine in vivo: Reaction Sites in Rat Liver DNA and the Significance of their Relative Stabilities

The reaction of the hepatocarcinogen N,N-dimethylnitrosamine has been compared with that of methyl methanesulphonate, a methylating agent which is not a liver carcinogen. Consistent differences have been observed in the reaction of rat liver DNA in vivo with these agents; O(6)-alkylation and the production of unidentified acid-labile products were distinctive features of the reaction with the carcinogenic nitroso compound but were undetectable or in low yield, respectively, after reaction with the alkyl sulphonate. Evidence has been obtained for the excision of these reaction products in animals treated with the hepatocarcinogen and the significance of their relative stabilities is discussed.