Mechanism of Alkylation of Nucleic Acids by Nitrosodimethylamine

Abstract

SINCE it was discovered¹ that nitrosodimethylamine givdes rise to alkylated nucleic acids in the liver when injected into rats, and that an alkylated base, 7-methylguanine, can be isolated from these nucleic acids, there has been much evidence of a correlation between carcinogenicity of N-nitrosamines and their transformation in vivo into an alkylating agent^2–4. There was evidence that the initial step in the conversion of the nitrosamine to an alkylating agent was an enzymatic oxidative dealkylation to a hypothetical monoalkylnitrosamine which was then converted to a diazoalkane or, by some other route, to a carbonium ion. No evidence of the production of a diazoalkane in this way has been presented, although this possibility has been widely postulated^5–8.