Nitrosamides, carcinogenicity

There is much evidence to suggest that carcinogenic N-nitros-amines are metabolised by an oxidative process to produce an alkylating agent (J f2) One potential metabolite is therefore the corresponding N-nitrosamide resulting from 2-electron oxidation at the oc-carbon atom, and, indeed, such compounds appear to induce tumours at the site of application without metabolic activation (3) It follows that the chemical properties of N-nitrosamides are relevant to the etiology of cancer ... 

The class of Il-nitroso compounds (l e , nitrosamines and nitrosamides) is currently considered a unique group that includes members with remarkable carcinogenic properties. Because of their potency and almost ubiquitous presence in... 

NOC constitute a large category of genotoxic chemical carcinogens occurring in human diet and are known to induce cancer in experimental animals. Nitrosamines are generally found in foods since they are more stable than nitrosamides. Some NOC precursors do not act directly but must be converted to other nitrosation species. 

Aside from the explosive hazard of A-nitrosamides, it also has been observed that many A-nitroso compounds have a serious physiological effect on mucous membranes and on the skin. Apparently, this corrosive action is not observed in the case of A,A -dinitroso-A,A -dimethyloxalamide [37a, b]. Even so, considering that some A-nitroso compounds are reputed to be carcinogenic, due care should be exercised in the handling of all nitroso compounds. 

Table 14.13 Critical structural feature which can affect the carcinogenicity of N-nitrosamides.

Zimmermann, F.K., Schwaier, R. von Laer, U. (1966) Mitotic recombination induced in Saccharomyces cerevisiae with nitrous acid, diethyl sulfate and carcinogenic, alkylating nitrosamides. Z. Vererbungsl., 98, 230-246... 

Ar-Nitroso compounds. All nitrosamines [R -N(NO)-R] and nitrosamides [R -N(NO)COR] should be regarded as potentially powerful carcinogens, since most compounds of these types have been shown to possess high activity in experimental animals. The following are some of the more likely to be encountered in the laboratory. 

Castegnaro, M. et al., Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes Some N-Nitrosamides, No. 55, IARC Scientific Publications, Lyon, 1983, p. 51. 

MMH and its precursor metabolite nitrosamide are low-grade carcinogens in experimental animals. How this relates to chronic, subacute consumption of this substance in mushrooms is unknown. 

The nitrosamines and nitrosamides are an important class of chemicals since a large number have been found to be carcinogenic. Nitrosamines require metabolic activation by target tissue microsomal mixed-function oxidases. 

Unlike polycyclic aromatic hydrocarbons, nitrosamines require only the first activation step which forms a hydroxylated intermediate that is sufficiently unstable to spontaneously decompose and generate a reactive carbonium which can rapidly alkylate target macromolecules in the cell. In contrast, nitrosamides do not require metabolic activation because of inherent chemical instability in aqueous solution. Nitrosamides decompose at physiological pH nonenzymatically to produce the same class of reactive electrophiles as the nitrosamines. Although the actual target site for nitroso carcinogens is not yet elucidated, a number of alkylation sites in DNA are known such as 0 -CH3-G, 7-CH3-G, and 3-CH3-A (2). 

Using this approach, methods were established for the degradation of selected compounds in the following seven classes of chemical carcinogens aflatoxins, nitrosamines, nitrosamides, polycyclic aromatic hydrocarbons, hydrazines, haloethers and aromatic amines. A first study was also set up to investigate methods of degradation of some antineoplastic agents,... 

Lunn, G., Sansone, E. B., Andrews, A. W., Castegnaro, M., Malaveille, C., Michelon, J., Brouet, I., Keefer, L. Destruction of carcinogenic and mutagenic N-nitrosamides in laboratory wastes, in A-Nitroso Compounds Occurrence Biological Effects and Relevance to Human Cancer (lARC Scientific Publications No. 57) (eds.) O Neill, I. K., von Borstel, R. C., Miller, C. T., Long,... 

Thanks to its characteristics colourless and odourless, easily soluble in water and alcohol, low toxicity, good skin compatibility, broad effective spectrum , Bronopol is being used on a large scale as a preservative for cosmetics and pharmaceuticals (concentrations 0 01-01%). It is listed in the EC list of preservatives allowed for the in-can protection of cosmetics (max. authorized concentration 01% limitations and requirements avoid formation of nitrosamines). Since it is in acidic solutions that Bronopol features the highest stability, weakly acidic media are the ideal field of application. In neutral or weakly alkaline formulations there is a risk that Bronopol releases nitrite (see above) which, with defined amines and amides, forms nitrosamines and nitrosamides which are regarded as carcinogens. 

When phenolics are added to nitrosation mixtures, C-nitroso derivatives could be formed. The question must be raised as to their genotoxic or carcinogenic properties. It would be an act of folly to use phenolics as inhibitors of mutagenic nitrosamines, nitrosamides or nitrosoalkylureas and, in the course of this process, create equally or even more active C-nitroso phenolics. Only scanty information is available on this issue. The mutagenicity of p-nitrosophenol is higher than that of phenol in the S, typhi-... 

Nitrosamines and nitrosamides are powerful carcinogens. They are obtained from secondary... 

The most salient commonality among the 210 carcinogens that are positive in Salmonella is the electrophilicity that is intrinsic to the molecule or introduced by enzymatic modification. The former can be thought of as ultimate mutagens and include known or presumable alkylating and acylating agents diazo compounds, nitrosamides, nitrosoureas, dimethylcarbamyl chloride, diaryl alkynyl carbamates, aziridines, oxiranes, thiirane,... 

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