Alkylation of Rat Liver Nucleic Acids Not Related to Carcinogenesis by N-Nitrosamines23

Abstract

The supposed relationship between carcinogenesis by N-nitrosamines and their conversion in vivo to an alkylating agent that alkylates nucleic acids in target organs was investigated. Rats were given single treatments with tritium-labeled nitrosoazetidine, nitrosohexamethyleneimine, nitrosomethylaniline, and nitrosomethylcyclohexylamine. DNA and RNA were isolated from liver and hydrolyzed in acid and the products separated by ion-exchange chromatography. The fractions were assayed for radioactivity and a peak of radioactivity was sought that did not correspond with guanine or adenine, as evidence of alkylation. None of the DNA's contained an alkylated base derived from the nitrosamine. Such an alkylated base was in the liver RNA from animals treated with the liver carcinogen nitrosoazetidine, but the liver RNA from animals treated with the liver carcinogen nitrosohexamethyleneimine contained no such alkylated base. On the other hand, nitrosomethylcyclohexylamine, though not a liver carcinogen, did give rise to an alkylated base in liver RNA, and this base was identified as 7-methylguanine by mass spectrometry. No alkylated base was detected in liver RNA of rats treated with nitrosomethylaniline. These results suggest that in vivo alkylation of nucleic acids by cyclic N-nitrosamines might be unrelated to carcinogenesis by these compounds.