Induction of reproductive system tumors in mice by N6-(methylnitroso)-adenosine and a tumorigenic effect of its combined precursors

Abstract

Interaction of the naturally-occurring nucleoside, N⁶-methyl adenosine, with nitrite, a reaction that occurs readily under acidic conditions, results in the formation of a nitrosamine, N⁶-(methylnitroso) adenosine [m⁶(NO)Ado]. This nitrosamine was given in the drinking water (1 mM solution) of non-inbred Swiss mice from 3 weeks of age until death. It caused a significant increase in the incidence of primary lung tumors, compared with controls. It also induced reproductive tract tumors in 80% of the exposed females, including mammary tumors in 60% and uterine tumors in 25%. The precursors of m⁶(NO) Ado, m⁶Ado and nitrite, did not elevate tumor incidence when given singly, but when administered together resulted in a significant increase in numbers of lung tumors in the males. The nitrosamine base, N⁶-(methylnitroso)adenine, was found to be a less potent carcinogen than m⁶(NO)Ado, causing lung tumors only in males and possibly a few mammary tumors in females. These results indicate the in vivo formation of a carcinogen from m⁶Ado and nitrite, and show that m⁶(NO)Ado induces neoplasms in the reproductive system of mice, an unusual target for a N-nitroso carcinogen.