Studies of alkylation of nucleic acids in rats by cyclic nitrosamines.

Five cyclic nitrosamines, nitrosoazetidine, nitrosopyrrolidine, nitrosopiperidine, nitrosomorpholine, and dinitrosopiperazine, labeled with deuterium and tritium, were injected into rats and then the nucleic acids of the liver were examined for the presence of alkylated bases derived from the nitrosamines. A semiquantitative mass spectrometric method able to detect 25 ng of a base was used. No deuterium-containing alkylated base was detected, although a small radioactive peak was present in the liver RNA from nitrosomorpholine-treated rats. Nitrosomethylcyclohexylamine gave rise to a deuterium-labeled (—CD3)7-methylguanine in the liver nucleic acids, showing that diazomethane was not an intermediate in its formation, but not in the esophagus nucleic acids, although esophagus is a target organ for this nitrosamine and liver is not. The expected correlation between carcinogenesis by these nitrosamines and alkylation of nucleic acids in vivo was not seen.