Nitroso compounds formation

Inhibition of Nitrosamine Formation. Nitrites can react with secondary amines and A/-substituted amides under the acidic conditions of the stomach to form /V-nitrosamines and A/-nitrosamides. These compounds are collectively called N-nitroso compounds. There is strong circumstantial evidence that in vivo A/-nitroso compounds production contributes to the etiology of cancer of the stomach (135,136), esophagus (136,137), and nasopharynx (136,138). Ascorbic acid consumption is negatively correlated with the incidence of these cancers, due to ascorbic acid inhibition of in vivo A/-nitroso compound formation (139). The concentration of A/-nitroso compounds formed in the stomach depends on the nitrate and nitrite intake. 

Control of N-nitroso compounds as carcinogenic agents so far has rested on agents that can block their formation. It is the intent of this paper to briefly review some of the studies which have been performed on the use of blocking agents to prevent N-nitroso compound formation and describe some recent observations on the mechanism by which these agents function. 

Ascorbic acid and alpha-tocopherol are effective blocking agents against N-nitroso compound formation. Ascorbic acid is effective particularly in aqueous media, and tocopherol effective particularly in lipid phases. They should be used in conjunction due to the mutually complementary actions of the two vitamins in blocking nitrosamine formation in both aqueous and lipid media. 

The bulk of this paper will be concerned with the prospects of Ji-nitroso compound formation in the environment, and with environmental behaviors of selected nitroso compounds, as best we can describe or predict them from experimental work completed thus far. Obviously, once in the environment, a compound will to a large extent be subject to the same conditions whether it was formed there or introduced as a pesticide contaminant, and in this manuscript no attempt to differentiate between the two modes of introduction has been made. Such distinctions could, however, influence the location of a compound in the environment—say on a plant or soil surface if sprayed with a pesticide, admixed with soil if transported by leaching, etc., and some of the experiments cited will have been conceived with one or the other of the introduction modes in mind. 

Tea exerts a relatively strong inhibitory potency for N-nitroso compound formation both in vitro and in humans. The active constituents may be related to their polyphenols content, especially the tea catechin derivatives [25]. 

Scheme 7.3 Alternative methods of C-acyl nitroso compound formation.

S- Nitroso compounds, formation, reactions and biological activity... 

It has also been demonstrated recently that the nitration of phenols in the presence of nitrous acid does not proceed by initial C-nitroso-compound formation (Ross et al., 1980). Product yields and orthoipara ratios were measured for the reaction of phenol with nitric acid alone, nitrous acid alone, and with both nitric and nitrous acid. The results for nitration could not be interpreted in terms of initial formation of 4-nitrosophenol but there was... 

Ascorbic acid is known to inhibit the nitrosation of secondary amines. A computer model has been developed to predict the amount of nitrosamine formed under conditions that are experimentally inaccessible. The computer-calculated rates for N-nitrosomorpholine formation using rate and equilibrium constants from the literature agree well with experimental values in the absence of and presence of ascorbic acid under anaerobic conditions. In the aerobic system the inhibitory efficiency of ascorbic acid is lower, and the nature of the interactions among the various components of the mixtures is less well understood. The use of ascorbic acid for inhibition of N-nitroso compound formation both in vitro and in vivo is briefly reviewed. 

Hoffmann, D., J.D. Adams, J.J. Piade, and S.S. Hecht Chemical studies on tobacco smoke. LXVItl. Analysis of volatile and tobacco-specific nitrosamines in tobacco products in V-Nitroso compounds Formation and occurrence, edited by E.A. Walker, L. Griciute, M. Castegnaro, and M. Borszonyi, lARC, Lyon, France, lARC Sci. Publ. No. 31 (1980) 507-514. 

Mirvish, S.S. Effect of vitamin C and E on A-nitroso compound formation, carcinogenesis and cancer Cancer 58 (1986) 1842-1850. 

Mirvish, S.S. Ascorbic acid inhibition of A-nitroso compound formation in chemical, food and biological systems in Inhibition of tumor induction and development, edited by M.S. Zedeck and M. Lipkin, Plenum Publishing, New York, NY (1981) 101-126. 

Mirvish, S.S., Effects of vitamins C and E on N-nitroso compound formation, carcinogenesis, and cancer. Cancer, 58,1842,1986. 

Mirvish, S. S., 1994, Experimental evidence for inhibition of N-nitroso compound formation as a factor in the negative correlation between vitamin C consumption and the incidence of certain cancers. Cancer Res. 54 81948-81951. 

Hoffsommer, J.C., Glover, D.J. and Elban, W.L. (1985) Quantitative Evidence for Nitroso Compound Formation in Drop-Weight Impacted RDX Crystals Journal of Energetic Materials 3, 149-167. 

Pourazrang, H., A. A. Moazzami, and B. S. Fazly Bazzaz. 2002. Inhibition of mutagenic N nitroso compound formation in sausage samples by using L-ascorbic acid and a-tocopherol. Meat Sci. 62 479-483. 

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