Decomposition reactions of (hydroxyalkyl)nitrosoureas and related compounds: possible relationship to carcinogenicity

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Abstract
(Hydroxyalkyl)nitrosoureas and the related cyclic carbamates N-nitrosooxazolidones are potent carcinogens. The decompositions of 4 such compounds, 1-nitroso-1-(2-hydroxyethyl)urea, 3-nitrosooxazolid-2-one, 1-nitroso-1-(2-hydroxypropyl)urea and 5-methyl-3-nitrosooxazolid-2-one, in aqueous buffers at physiological pH were studied to determine if any obvious differences in decomposition pathways could account for the variety of tumors obtained from these 4 compounds. The products predicted by the literature mechanisms for nitrosourea and nitrosooxazolidone decompositions (which were derived from experiments at pH 10-12) were indeed the products formed, including glycols, active carbonyl compounds, epoxides, and, from the oxazolidones, cyclic carbonates. In pH 6.4-7.4, buffer epoxides were stable reaction products. In the presence of hepatocytes, most of the epoxide was converted to glycol. The analytical methods developed were then applied to the analysis of the decomposition products of some related dialkylnitrosoureas, and similar results were obtained. The formation of chemically reactive secondary products and the possible relevance of these results to carcinogenesis studies are discussed.

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