N6-(Methylnitroso)adenosine: a carcinogen from a nucleic acid component

Substituted aminopurines in nucleic acids may be nitrosated to yield carcinogenic nitrosaminopurines. To investigate this possibility, we studied the nitrosation of N6-methyladenosine under conditions simulating the gastric environment. We administered the product of this reaction, N6-(methylnitroso)adenosine (m6(NO)Ado), parenterally and orally to mice. A high incidence of thymic lymphomas, lung adenomas and some liver tumours were found in mice given m6(NO)Ado i.p. during early life. Oral administration of m6(NO)Ado to adult mice resulted in the formation of reproductive system tumours in 80% of the exposed female mice, as well as lung tumours in both sexes. The precursors of m6(NO)Ado (m6Ado and nitrite) did not elevate tumour incidence when given separately, but resulted in a significant increase in numbers of lung tumours in males when administered together. The nitrosamine base, N6-(methylnitroso)-adenine, was found to be a less potent carcinogen than m6(NO)Ado, causing lung tumours only in males and possibly a few mammary tumours in females. These results indicate the in vivo formation of a carcinogen from the precursors, N6-methyladenosine and nitrite, and show that m6(NO)Ado induces neoplasms in the reproductive system of mice, an unusual target for an N-nitroso carcinogen. Complete inhibition of nitrosaminopurine formation in vitro was obtained with ascorbic acid.