Nitrosamines and Human Cancer: Some Implications of Basic Research

  • Peter N. Magee


The nitrosamines belong to the class of N-nitroso compounds which also includes nitrosoalkylureas and nitroso-N-alkylcarbamates, conveniently described as nitrosamides, and nitrosamidines. The chemical structures of some examples of these compounds are shown in Figure 1. N-nitroso compounds undergo photochemical decomposition when exposed to ultraviolet light but the nitrosamines are chemically stable under physiological conditions in the absence of light. The nitrosamides and nitrosamidines, on the other hand, decompose rapidly at alkaline pH and, in some cases, in the presence of sulfhydryl compounds, to yield alkylating products. Decomposition may also occur more slowly at neutrality. These differences in chemical stability have profound effects on the biological activities of the compounds. More than 300 N-nitroso compounds are known to be carcinogenic and their chemical properties and biological activities, which include cytotoxicity, carcinogenicity, mutagenicity, teratogenicity and use in the chemotherapy of human cancer, have been extensively reviewed (1–7). Most studies of the acute toxicity of the nitrosamines have been carried out with the shorter chain dialkyl and simpler cyclic compounds such as dimethyl-and diethylnitrosamine and N-nitrosomorpholine which are selectively hepatotoxic while the nitrosamides and nitrosamidines cause tissue and cellular injury at the site of application and, in varying degree, to organs with rapid cell turnover such as the bone marrow, lymphoid tissue and intestine. As will be discussed later, these differences in tissue and organ specificity may reflect the requirement of the nitrosamines for metabolic activation and the absence of this requirement by the nitrosamides. More than 300 N-nitroso compounds have been found to be carcinogenic (4) and, so far all species adequately tested have proven to be susceptible to the carcinogenic action of one or more nitrosamines (8,9), N-nitrosodiethylamine having been the compound used most often. The susceptible species have included monkeys, dogs, cats, pigs, and the usual laboratory rodents, fish, amphibia, and most recently, snakes (9). The compounds are equally effective as mutagens in all of the usual test systems, with the nitrosamines requiring an enzyme system, usually the so-called liver S-9 mix of the Ames test, whereas the nitrosamides and nitrosamidines are direct acting mutagens (5–7). Several of the smaller molecular weight compounds are alkylating agents, the nitrosamines requiring metabolic activation and the nitrosamides acting directly to alkylate DNA and other cellular constituents.


Nasopharyngeal Carcinoma Smokeless Tobacco Nitroso Compound Smokeless Tobacco Product Salted Fish 
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© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Peter N. Magee
    • 1
  1. 1.Fels Research Institute and Department of PathologyTemple University School of MedicinePhiladelphiaUSA

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