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

  • Chapter
Inhibition of Tumor Induction and Development

Abstract

Cameron et al. (1979) have reviewed the effect of ascorbic acid (ASC) on tumor growth and progression and on carcinogenesis in general. Five years ago (Mirvish, 1975a), I reviewed the subject of this chapter, and the present review covers reports up to the middle of 1979.

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References

  • Archer, M. D., Tannenbaum, S. R., Fan, T. Y., and Weisman, M., 1975, Reaction of nitrite with ascorbate and its relation to nitrosamine formation, J. Natl. Cancer Inst. 54:1203.

    Google Scholar 

  • Astill, B. D., and Mulligan, L. T., 1977, Phenolic antioxidants and the inhibition of hepatotoxicity from iV-dimethylnitrosamine formed in situ in the rat stomach, Food Cosmet. Toxicol. 15:167.

    Article  Google Scholar 

  • Birdsall, J. J., 1977, JV-Nitrosopyrrolidine in bacon obtained from 10 commercial bacon production plants, in: Proceedings of the 2nd International Symposium on Nitrite in Meat Products, Central Agricultural Publication Documentation ( B. J. Linbergen, and B. Krol, eds.), pp. 211–213, Pudoc Press, Wageningen, Netherlands.

    Google Scholar 

  • Bruce, W. R., Varghese, A. J., Wang, S., and Dion, P., 1979, The endogenous production of nitroso compounds in the colon and cancer at that site, in: Naturally Occurring Carcinogens —Mutagens and Modulators of Carcinogenesis ( E. C. Miller, J. A. Miller, I. Hirono, T. Sugimura, and S. Takayama, eds.), pp. 221–228, University Park Press, Baltimore.

    Google Scholar 

  • Bunton, C. A., Dahn, H., and Loewe, L., 1959, Oxidation of ascorbic acid and similar substances by nitrous acid, Nature 183:163.

    Article  Google Scholar 

  • Cameron, E., Pauling, L., and Leibovitz, B., 1979, Ascorbic acid and cancer: A review, Cancer Res. 39:663.

    Google Scholar 

  • Cardesa, A., Mirvish, S. S., Haven, G. T., and Shubik, P., 1974, Inhibitory effect of ascorbic acid on the acute toxicity of dimethylamine plus nitrite in the rat, Proc. Soc. Exp. Biol. Med. 145:124.

    Google Scholar 

  • Challis, B. C., and Bartlett, C. D., 1975, Possible cocarcinogenic effects of coffee constituents, Nature 254:532.

    Article  Google Scholar 

  • Challis, B. C., and Kyrtopoulos, S. A., 1977, Rapid formation of carcinogenic JV-nitrosamines in aqueous alkaline solutions, Br. J. Cancer 35:693.

    Article  Google Scholar 

  • Challis, B. C., Edwards, A., Hunma, R. R., Kyrtopoulos, S. A., and Outram, J. R., 1978, Rapid formation of jV-nitrosamines from nitrogen oxides under neutral and alkaline conditions, in: Environmental Aspects of N-Nitroso Compounds ( E. A. Walker, M. Castegnaro, L. Griciute, and E. R. Lyle, eds.), pp. 127–142, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Chan, W. C., and Fong, Y. Y., 1977, Ascorbic acid prevents liver tumor production by aminopyrine and nitrite in the rat, Int. J. Cancer 20:268.

    Article  Google Scholar 

  • Chang, S. F., Harrington, G. W., Rothstein, M., Shergalis, W. A., Swern, D., and Vohra, S. K., 1979, Accelerating effect of ascorbic acid on W-nitrosamine formation and nitrosation by oxyhyponitrite, Cancer Res. 39:3871.

    Google Scholar 

  • Coordinating Group for Research on the Etiology of Esophageal Cancer of North China, 1974, The Epidemiology of Esophageal Cancer in North China and Preliminary Results in the Investigation of its Etiological Factors, National Academy of Medical Sciences, Peking.

    Google Scholar 

  • Cuello, C., Correa, P., Haenszel, W., Gordillo, G., Brown, C., Archer, M., and Tannenbaum, S., 1976, Gastric cancer in Colombia. I. Cancer risk and suspect environmental agents, J. Natl. Cancer Inst. 57:1015.

    Google Scholar 

  • Dahn, H., Loewe, L., and Bunton, C. A., 1960, Uber die Oxydation von Ascorbinsaure durch salpetrige Saure. Teil VI: Ubersicht und Diskussion der Ergebnisse, Helv. Chim. Acta 43:320.

    Article  Google Scholar 

  • Day, N. E., 1975, Some aspects of the epidemiology of esophageal cancer, Cancer Res. 35:3304.

    Google Scholar 

  • Edgar, J. A., 1974, Ascorbic acid and biological alkylating agents, Nature 248:136.

    Article  Google Scholar 

  • Fan, T. Y., and Tannenbaum, S. R., 1973, Natural inhibitors of nitrosation reactions: The concept of available nitrite, J. Food Sci. 38:1067.

    Article  Google Scholar 

  • Fiddler, W., Pensabene, J. W., Piotrowski, E. G., Doerr, R. C., and Wasserman, A. E., 1973, Use of sodium ascorbate or erythorbate to inhibit formation of A-nitrosodimethylamine in frankfurters, J. Food Sci. 38:1084.

    Article  Google Scholar 

  • Fong, Y. Y., and Chan, W. C., 1976, The effect of ascorbate on amine-nitrite carcinogenicity, in: Environmental N-Nitroso Compounds: Analysis and Formation ( E. A. Walker, P. Bogovski, and L. Griciute, eds.), pp. 461–464, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Galloway, S. M., and Painter, R. B., 1979, Vitamin C is positive in the DNA synthesis inhibition and sister-chromatid exchange tests, Mutat. Res. 60:321.

    Article  Google Scholar 

  • Gray, J. I., and Dugan, L. R., 1975, Inhibition of iV-nitrosamine formation in model food systems, J. Food Sci. 40:981.

    Article  Google Scholar 

  • Greenblatt, M., 1973, Ascorbic acid blocking of aminopyrine nitrosation in NZO/B1 mice, J. Natl. Cancer Inst. 50:1055.

    Google Scholar 

  • Greenblatt, M.,and Mirvish, S. S., 1973, Dose-response studies with concurrent administration of piperazine and sodium nitrite to strain A mice, J. Natl. Cancer Inst. 50:119.

    Google Scholar 

  • Greenblatt, M., Mirvish, S. S., and So, B. T., 1971, Nitrosamine studies: Induction of lung adenomas by concurrent administration of sodium nitrite and secondary amines in Swiss mice, J. Natl. Cancer Inst. 46:1029.

    Google Scholar 

  • Guttenplan, J. B., 1977, Inhibition by L-ascorbate of bacterial mutagenesis induced by two iV-nitroso compounds, Nature 268:368.

    Article  Google Scholar 

  • Guttenplan, J. B., 1978, Mechanisms of inhibition by ascorbate of microbial mutagenesis induced by #-nitroso compounds, Cancer Res. 38:2018.

    Google Scholar 

  • Haenszel, W., and Correa, P., 1975, Developments in the epidemiology of stomach cancer over the past decade, Cancer Res. 35:3452.

    Google Scholar 

  • Harman, D., 1962, Role of free radicals in mutation, cancer, aging and the maintenance of life, Radiat. Res. 16:753.

    Article  Google Scholar 

  • Ho, J. H. C., 1978, An epidemiologic and clinical study of nasopharyngeal carcinoma, Int. J. Radiat. Oncol. Biol. Biophys. 4:183.

    Article  Google Scholar 

  • Hormozdiari, H., Day, N. E., Aramesh, B., and Mahboubi, E., 1975, Dietary factors and esophageal cancer in the Caspian littoral of Iran, Cancer Res. 35:3493.

    Google Scholar 

  • Ivankovic, S., Preussmann, R., Schmahl, D., and Zeller, J., 1973a, Verhiitung von Nitrosamidbedingtem Hydrocephalus durch Ascorbinsaure nach praenataler Gabe von Athylharnstoff und Nitrit an Ratten, Z. Krebsforsch. 79:145.

    Google Scholar 

  • Ivankovic, S., Zeller, W. J., Schmahl, D., and Preussmann, R., 1973b, Verhinderungder pranatal carcinogenen Wirkung von Athylharnstoff und Nitrit durch Ascorbinsaure, Naturwissenschaften 60:525.

    Article  Google Scholar 

  • Ivankovic, S., Preussmann, R., Schmahl, D., and Zeller, J. W., 1974, Prevention by ascorbic acid of in vivo formation of iV-nitroso compounds, in: N-Nitroso Compounds in the Environment ( P. Bogovski and E. A. Walker, eds.), pp. 101–102, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Kamm, J. J., Dashman, T., Conney, A. H., and Burns, J. J., 1973, Protective effects of ascorbic acid on hepatotoxicity caused by sodium nitrite plus aminopyrine, Proc. Natl. Acad. Sci. USA 1 0:741.

    Google Scholar 

  • Kamm, J. J., Dashman, T., Conney, A. H., and Burns, J. J., 1975, Effect of ascorbic acid on amine-nitrite toxicity, Ann. N. Y. Acad. Sci., 258:169.

    Article  Google Scholar 

  • Kamm, J. J., Dashman, T., Newmark, H., and Mergens, W. J., 1977, Inhibition of amine-nitrite hepatotoxicity by alpha-tocopherol, Toxicol. Appl. Pharmacol. 41:575.

    Article  Google Scholar 

  • Khan, M. M. T., and Martell, A. E., 1967, Metal ion and metal chelate catalyzed oxidation of ascorbic acid by molecular oxygen. I. Cupric and ferric ion catalyzed oxidation, J. Am. Chem. Soc. 89:4176.

    Article  Google Scholar 

  • Kinawi, A., and Schuster, T., 1978, Reaktionskinetische Untersuchengen zur Entstehung von N- Nitrosoephedrin in vitro and in vivo, Arzneim. Forsch. 28:219.

    Google Scholar 

  • Kokatnur, M. G., Murray, M. L., and Correa, P., 1978, Mutagenic properties of nitrosated spermidine, Proc. Soc. Exp. Biol. Med. 158:85.

    Google Scholar 

  • Lijinsky, W., and Greenblatt, M., 1972, Carcinogen dimethylnitrosamine produced in vivo from nitrite and aminopyrine, Nature [New Biol.] 236:177.

    Article  Google Scholar 

  • Lijinsky, W., Conrad, E., and Bogart, R.V.D., 1972, Formation of carcinogenic nitrosamines by interaction of drugs with nitrite, in: N-Nitroso Compounds—Analysis and Formation ( P. Bogovski, R. Preussmann, and E. A. Walker, eds.), pp. 130–133, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Lo, L. W., and Stich, H. F., 1978, The use of short-term tests to measure the preventive action of reducing agents on formation and activation of carcinogenic nitroso compounds, Mutat. Res. 57:57.

    Google Scholar 

  • Massey, R. C., Crews, C., Davies, R., and McWeeny, D. J., 1978, A study of the competitive nitrosations of pyrrolidine, ascorbic acid, cysteine and /7-cresol in a protein-based model system, J. Sci. Food Agric. 29:815.

    Article  Google Scholar 

  • Meinsma, L., 1964, Voeding en kanker, Voeding 25:357.

    Google Scholar 

  • Mergens, W. J., Kamm, J. J., Newmark, H. L., Fiddler, W., and Pensabene, J., 1978, Alpha-tocopherol: Use in preventing nitrosamine formation, in: Environmental Aspects of N-Nitroso Compounds ( E. A. Walker, M. Castegnaro, L. Griciute, and R. E. Lyle, eds.), pp. 199–212, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Mergens, W. J., Vane, F. M., Tannebaum, S. R., Green, L., and Skipper, P. L., 1979, In vitro nitrosation of methapyrilene, J. Pharm. Sci. 68:827.

    Google Scholar 

  • Mirvish, S. S., 1971, Kinetics of nitrosamide formation from alkylureas, N-alkylurethans and alkylguanidines: Possible implications for the etiology of human gastric cancer, J. Natl. Cancer Inst. 46:1183.

    Google Scholar 

  • Mirvish, S. S., 1975a, Blocking the formation of TV-nitroso compounds with ascorbic acid in vitro and in vivo, Ann. N. Y. Acad. Sci. 258:175.

    Article  Google Scholar 

  • Mirvish, S. S., 1975b, Formation of W-nitroso compounds: Chemistry, kinetics, and in vivo occurrence, Toxicol. Appl. Pharmacol 31:325.

    Article  Google Scholar 

  • Mirvish, S. S., 1977, iV-Nitroso compounds: Their chemical and in vivo formation and possible importance as environmental carcinogens. J. Toxicol. Environ. Health 2:1267.

    Google Scholar 

  • Mirvish, S., 1981, in: Cancer: Achievements, Challenges and Prospects for the 1980’s (J. H. Burchenal and H. F. Oettgen, eds.), pp. 557–587, Grune & Stratton, New York.

    Google Scholar 

  • Mirvish, S. S., and Shubik, P., 1974, Ascorbic acid and nitrosamines, Nature 250:684.

    Article  Google Scholar 

  • Mirvish, S. S., Wallcave, L., Eagen, M., and Shubik, P., 1972a, Ascorbate-nitrite reaction: Possible means of blocking the formation of carcinogenic iV-nitroso compounds, Science 177:65.

    Article  Google Scholar 

  • Mirvish, S. S., Greenblatt, M., and Kommineni, V. R. C., 1972b, Nitrosamide formation in vivo: Induction of lung adenomas in Swiss mice by concurrent feeding of nitrite and methylurea or ethylurea, J. Natl. Cancer Inst. 48:1311.

    Google Scholar 

  • Mirvish, S. S., Gold, B., Eagen, M., and Arnold, S., 1974, Kinetics of the nitrosation of aminopyrine to give dimethylnitrosamine, Z. Krebsforsch. 82:259.

    Article  Google Scholar 

  • Mirvish, S. S., Cardesa, A., Wallcave, L., and Shubik, P., 1975, Induction of mouse lung adenomas by amines and ureas plus nitrite and by W-nitroso compounds: Effect of nitrite dose and of ascorbate, gallate, thiocyanate, and caffeine, J. Natl. Cancer Inst. 55:633.

    Google Scholar 

  • Mirvish, S. S., Pelfrene, A., Garcia, H., and Shubik, P., 1976, Effect of sodium ascorbate on tumor induction in rats treated with morpholine and sodium nitrite, and with nitrosomorpholine, Cancer Lett. 2:101.

    Article  Google Scholar 

  • Mirvish, S. S., Karlowski, K., Sams, J., and Arnold, S. D., 1978, Studies related to nitrosamide formation: Nitrosation in solvent: water and solvent systems, nitrosomethylurea formation in the rat stomach, and analysis of a fish product for ureas, in: Environmental Aspects of N-Nitroso Compounds ( E. A. Walker, M. Castegnaro, L. Griciute, and R. E. Lyle, eds.), pp. 161–174, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Mottram, D. S., and Patterson, R. L. S., 1977, The effect of ascorbate reductants on iV-nitrosamine formation in a model system resembling bacon fat, J. Sci. Food Agric. 28:352.

    Article  Google Scholar 

  • Newberne, P. M., 1979, Nitrite promotes lymphoma incidence in rats, Science 204:1079.

    Article  Google Scholar 

  • Pensabene, J. W., Fiddler, W., Feinberg, J., and Wasserman, A. E., 1976, Evaluation of ascorbyl monoesters for the inhibition of nitrosopyrrolidine formation in a model system, J. Food Sci. 41:199.

    Article  Google Scholar 

  • Pipkin, G. E., Schlegel, J. U., Nishimura, R., and Shultz, G. N., 1969, Inhibitory effect of L-ascorbate on tumor formation in urinary bladders implanted with 3-hydroxyanthranilic acid, Proc. Soc. Exp. Biol. Med. 131:522.

    Google Scholar 

  • Preda, N., Popa, L., and Galea, V., 1976, iV-Nitroso compound formation by chlordiazepoxide and nitrite interaction in vitro and in vivo: Protective action of ascorbic acid, in: Environmental N-Nitroso Compounds: Analysis and Formation (E. A. Walker, P. Bogovski, and L. Griciute, eds.), pp. 301–304, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Ridd, J. H., 1961, Nitrosation, diazotisation, and deamination, Q. Rev. Chem. Soc. 15:418.

    Article  Google Scholar 

  • Roper, H., and Heyns, K., 1978, Possible nitrosodimethylamine formation in comparative in vitro nitrosation experiments with six different tetracycline antibiotics, in: Environmental Aspects of N-Nitroso Compounds ( E. A. Walker, M. Castegnaro, L. Griciute, and R. E. Lyle, eds.), pp. 219–237, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Ruddell, W. S., Blendis, L. M.,and Walters, C. L., 1977, Nitrite and thiocyanate in the fasting and secreting stomach and in saliva, Gut 18:73.

    Google Scholar 

  • Rustia, M., 1975, Inhibitory effect of sodium ascorbate on ethylurea and sodium nitrite carcinogenesis and negative findings in progeny after intestinal inoculation of precursors into pregnant hamsters, J. Natl. Cancer Inst. 55:1389.

    Google Scholar 

  • Sander, J., and Biirkle, G., 1969, Induktion maligner Tumoren bei Ratten durch gleichzeitige Verfuttenrung von Nitrit und sekindaren Aminen, Z. Krebsforsch. 73:54.

    Article  Google Scholar 

  • Sen. N. P., and Donaldson, B., 1974, The effect of ascorbic acid and glutathione on the formation of nitrosopiperazines from piperazine adipate and nitrite, in: N-Nitroso Compounds: Analysis and Formation ( P. Bogovski, E. A. Walker, and W. Davis, eds.), pp. 103–106, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Sen, N. P., Donaldson, B., Seaman, S., Iyengar, J. R., and Miles, W. F., 1976, Inhibition of nitrosamine formation in fried bacon by propyl gallate and L-ascorbyl palmitate, J. Agric. Food. Chem. 24:397.

    Article  Google Scholar 

  • Stich, H. F., Karim, J., Koropatnick, J., and Lo, L., 1976, Mutagenic action of ascorbic acid, Nature 260:722.

    Article  Google Scholar 

  • Synnett, J. A., Unger, I., and Strunz, G., 1975, On the reactions of NaN02 with ethyl urea in the presence and absence of ascorbic acid, Naturwissenschaften 62:138.

    Google Scholar 

  • Tanaka, K., Chung, K. C., Hayatsu, H., and Kada, T., 1978, Inhibition of nitrosamine formation in vitro by sorbic acid, Food Cosmet. Toxicol. 16:209.

    Article  Google Scholar 

  • Tannenbaum, S. R., Sinskey, A. J., Weisman, M., and Bishop, W., 1974, Nitrite in human saliva: Its possible relationship to nitrosamine formation, J. Natl. Cancer Inst. 53:19.

    Google Scholar 

  • Tannenbaum, S. R., Fett, D., Young, V. R., Land, P. D., and Bruce, W. R., 1978, Nitrite and nitrate are formed by endogenous synthesis in the human intestine, Science 200:1487.

    Article  Google Scholar 

  • Varghese, A. J., Land, P. C., Furrer, R., and Bruce, W. R., 1978, Non-volatile jV-nitroso compounds in human feces, in: Environmental Aspects of N-Nitroso Compounds ( E. A. Walker, M. Castegnaro, L. Griciute, and R. W. Lyle, eds.), pp. 257–264, International Agency for Research on Cancer, Lyon.

    Google Scholar 

  • Walters, C. L., Edwards, M. W., Elsey, T. S., and Martin, M., 1976, The effect of antioxidants on the production of volatile nitrosamines during the frying of bacon, Z. Lebensm. Unters. Forsch. 162:377.

    Article  Google Scholar 

  • Weisburger, J. H., 1977, Vitamin C and prevention of nitrosamine formation, Lancet 2:607.

    Article  Google Scholar 

  • Weisburger, J. H., 1979, Mechanism of action of diet as a carcinogen, Cancer 43:1987.

    Google Scholar 

  • Williams, D. L. H., 1978, Comparison of the efficiencies of ascorbic acid and sulphamic acid as nitrite traps, Food. Cosmet. Toxicol. 16:365.

    Article  Google Scholar 

  • Ziebarth, D., and Scheunig, G., 1976, Effects of some inhibitors on the nitrosation of drugs in human gastric juice, in: Environmental N-Nitroso Compounds: Analysis and Formation ( E. A. Walker, P. Bogovski, and L. Griciute, eds.), pp. 279–290, International Agency for Research on Cancer, Lyon.

    Google Scholar 

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Mirvish, S.S. (1981). Ascorbic Acid Inhibition of N-Nitroso Compound Formation in Chemical, Food, and Biological Systems. In: Zedeck, M.S., Lipkin, M. (eds) Inhibition of Tumor Induction and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9218-1_4

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