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.

Condensation products of amino acids and proteins with biologically active purines have been obtained to study their potential tumor inhibitory activity and as models for the preparation of conjugates with tumor specific antibodies. Among the new compounds are 2‐glycinyl‐6‐methylmercaptopurine (5), 2‐glycinyl‐6‐mercaptopurine (6), 2‐glycinyl‐6‐chloropurine (16), 2‐glycinyl‐6‐hydroxylaminopurine (18), 2‐glycinylpurine (8) and 2‐glycinyl‐6‐methylpurine (7). 9‐Alkylpurines led to new purine derivatives, such as 6‐chloro‐9H‐purine‐9‐acetic acid (22) and 6‐hydroxylamino‐9H‐purine‐9‐acetylhydroxamic acid (23). These derivatives were coupled to bovine serum albumin (BSA) to yield conjugates. The amino acid‐purines 6‐cysteinyl (27) and 6‐glutathionyl‐S‐purine 3‐oxide (28) were obtained from 6‐chloropurine 3‐oxide (26). Other protein‐purine 3‐oxide conjugates were obtained with 6‐mercaptopurine 3‐oxide (29) and 6‐bromomethylpurine 3‐oxide (33).

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