Ascorbic Acid Inhibition of N-Nitroso Compound Formation in Chemical, Food, and Biological Systems

Naturally Occurring Anticarcinogenic Substances in Foodstuffs

“…The inhibition of nitrosation by ascorbic acid/ascorbate (pKa=4.3) is most effective for slowly nitrosated amines such as dimethylamine and for those nitrosated at moderate velocities, such as morpholine and piperazine; in rapidly nitrosated amines such as N-methylaniline, inhibition is incomplete. Excellent reviews of this subject were presented by Mirvish (72,73). The current practice in the US is to add about 550 ppm sodium ascorbate or sodium erythorbate (sodium isoascorbate) in conjunction with 120 ppm nitrite to foods such as frankfurters.…”

“…Epidemiological studies show that enhanced incidence of stomach cancer is correlated with high nitrate content of the soil and/or drinking water in certain parts of the world (28,36), or the intake of salted, pickled, or smoked foods that contain nitrate, nitrosamines, or diazo compounds (152,154) . Adding nitrite to foodstuffs enhances color and inhibits the growth of Clostridium botulinum, but it also causes N-nitroso compounds to form in meats and meat products such as sausage and frankfurters and to form during the frying of bacon (73,82). Fermentation processes, including pickling and brewing, generate nitrite from nitrogenous precursors, as does the microbial activity occurring during nonre frigerated storage of certain foods (142,143).…”

“…Ascorbic acid was the first naturally occurring substance found to effectively block the formation of N-nitroso compounds (20,(72)(73)(74)(75). Ascorbic acid and, more so, the ascorbate anion (72) reduce N203 to nitric oxide, NO, thus decreasing the concentration of N203 available for nitrosation of amines and amides.…”

“…N-nitroso compounds are formed with great facility by the interaction of a NEOPLASIA nitro sating species such as nitrogen trioxide, N203, or dinitrogen tetroxide, N204, with primary, secondary, or tertiary amines, or with secondary amides (73). These reactions can occur in aqueous and organic media as well as in the gas phase.…”

Antimutagens and anticarcinogens: A survey of putative interceptor molecules

“…Ascorbate suppressed mutagenicity of malonaldehyde and P-propiolactone for Salmonella [Shamberger et al, 19791. Ascorbate directly inactivated inhibitory activity for recombination-deficient bacteria of the chemical mutagens ley et al, 19871 could be a result of abnormalities in the ascorbate vs. catalase/glutathione/peroxidase levels and the presence of free-transition metal ions in special circumstances [Speit et al, 1980;Frei et al, 19891. Dexon, captan, mitomycin C, 4-nitroquinoline oxide, and N-methyl-N'-nitro-N-nitrosoguanidine [Onitsuka et al, 1978; as cited in Kuroda, 19891, and ascorbate decreased mutagenicity of the latter compound for Salmonella [Jain et al, 19891. Besides being an important antioxidant, ascorbate reacts at acid pH with nitrite and thus blocks the in vitro and in vivo formation of mutagenic and carcinogenic N-nitroso compounds [Mirvish et al, 1972;Mirvish, 1981Mirvish, , 1986Kyrtopoulos, 19871. Recently, elegant in vivo experiments in rodents and humans using the N-nitrosoproline urinary excretion procedure developed by Ohshima and Bartsch [ 198 la,b] have confirmed suppositions from numerous in vitro studies; ascorbate clearly inhibits the endogenous formation of N-nitroso compounds, including nitrosoproline, in animals [Bartsch et al, 1988;Mackerness et al, 19891.…”