Induction of reproductive system tumors in mice by N6-(methylnitroso)-adenosine and a tumorigenic effect of its combined precursors.
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.
D000230:Adenocarcinoma / Q000139:chemically induced; D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D005260:Female; D007889:Leiomyoma / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009573:Nitrites; D009602:Nitrosamines / Q000138:chemical synthesis; D009603:Nitroso Compounds; D010051:Ovarian Neoplasms / Q000139:chemically induced*; D014594:Uterine Neoplasms / Q000139:chemically induced*
D009573:Nitrites; D009602:Nitrosamines; D009603:Nitroso Compounds; D000241:Adenosine