Abstract
N-nitroso compounds have been known since they were first synthesized in Germany in the mid-nineteenth century. They have been extensively used in organic synthesis, analytical chemistry and 1 research for over a century. However, in 1954, Barnes and Magee found that dimethylnitrosamine (DMN) produced liver toxicity in two men in the UK. Similarly, an outbreak of acute liver toxicity in sheep in Norway was traced to the formation of DMN in fish meal preserved by nitrite.2 These events prompted the early synthetic investigations of the N-nitroso compounds, particularly by groups headed by Magee in the UK and US, and Druckrey in Germany. Their work, and that of others, rapidly showed that the N-nitroso compounds, as a group, had enormous potential for carcinogenesis. This, in turn, has led to the current deep scientific interest in the analysis, formation, and occurrence of carcinogenic N-nitroso compounds in our food supply, polluted atmosphere, drinking water, beverages, cigarette smoke, cosmetics, industrial waste and by-products, and more recently to their formation in vivo.3,4,5 It is the intention of this paper to survey several aspects of these studies and address the use of ascorbic acid and alpha-tocopherol as blocking agents to prevent the formation of these potential human carcinogens.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
J. M. Barnes and P. N. Magee, Some toxic properties of dimethylnitrosamine, Brit. J. Industrial Med. 11:167 (1954).
F. Ender, G. Havre, A. Helgebostad, N. Koppang, R. Madsen, and L. Ceh, Insolation and identification of a hepatotoxic factor in herring meal produced from sodium nitrite preserved herring, Naturwissenschaften 24: 637 (1964).
D. H. Fine, R. Ross, D. P. Rounbehler, A. Silvergleid, and L. Song, Formation in vivo of volatile N-nitrosamines, Nature 265: 753 (1977).
R. M. Hicks, T. A. Gough, and C. L. Walters, Demonstration of the presence of nitrosamines in human urine: preliminary observations on a possible etiology for bladder cancer in association with chronic urinary tract infection, in: “Environmental Aspects of N-Nitroso Compounds,” E. A. Walker, M. Castegnaro, L. Griciute, R. E. Lyle, eds., IARC Publication #19, Lyon (1978).
L. Lakritz, A. Wasserman, R. Gates, and A. Spinelli, Preliminary observations on amines and nitrosamines in non-normal human gastric contents, in: “Environmental Aspects of N-Nitroso Compounds,” E. A. Walker, M. Castegnaro, L. Griciute, R. E. Lyle, eds., IARC Publication #19, Lyon (1978).
P. N. Magee and J. M. Barnes, Carcinogenic N-nitroso compounds, Adv. Cancer Res. 10:163 (1967).
B. Terracini, P. N. Magee, and J. M. Barnes, Hepatic pathology in rats on low dietary levels of dimethylnitrosamine, Br. J. Cancer 21:559 (1967).
D. Fine, F. Rufeh, and B. Gunther, A group specific procedure for the analysis of both volatile and non-volatile Nnitroso compounds in picogram amounts, Anal. Letters 6(8): 731 (1973).
H. Druckrey, R. Freissman, S. Ivankovic and D. Schmaehl, Organotropic carcinogenic effects of 65 different N-nitroso compounds on BD rats, Z. Krebsforschung 64:103 (1967).
H. Marquardt, F. Rufino, and J. H. Weisburger, Mutagenic activity of nitrite-treated foods: Human stomach cancer may be related to dietary factors, Science 196: 1000 (1977).
M. L. Douglas, B. L. Kabacoff, G. A. Anderson, and M. C. Cheng, The chemistry of nitrosamine formation, inhibition, and destruction, J. Soc. Cosmet. Chem. 29:581 (1978).
S. S. Mirvish, Formation of N-nitroso compounds. Chemistry, kinetics, and in vivo occurrence, Tox. Appl. Pharmacol.31:325 (1975).
J. H. Ridd, Nitrosation, Diazotization, and Deamination, Q. Rev. Chem. Soc. 15:418 (1961).
P. A. S. Smith and H. G. Pars, Nitrosative cleavage of N’, N’-dialkylhydrazides and tertiary amines, J. Org. Chem.24:1325 (1959).
P. A. S. Smith and R. N. Leoppky, Nitrosative cleavage of tertiary amines, J. Amer. Chem. Soc. 89:1147 (1967).
W. Fiddler, J. W. Pensabene, R. C. Doerr, and A. E. Wasserman, Formation of N-nitrosodimethylamine from naturally occurring quaternary ammonium compounds and tertiary amines, Nature 236: 307 (1972).
S. S. Mirvish, Kinetics of Nitrosamide Formation from alkylureas, N-alkylurethans, and alkylguanidines. Possible implications for the etiology of human gastric cancer, J. Nat. Cancer Inst. 46:1183 (1971).
S. S. Mirvish, Kinetics of N-nitrosation reactions in relation to tumorigenesis experiments with nitrite plus amines or urea, in: “N-Nitroso Compounds: Analysis and Formation,” P. Bogovski, R. Preussmann, E. A. Walker, eds., IARC Scientific Publications No. 3, Lyon (1974).
E. H. White, The chemistry of N-alkyl-N-nitrosamides. I. Methods of preparation, J. Amer. Chem. Soc. 77: 6008 (1955).
J. D. Okun and M. C. Archer, Kinetics of nitrosamine formation in the presence of micelle forming surfactants, J. Natl. Cancer Inst. 58(2):409 (1977).
J. J. Kamm, T. Dashman, A. H. Conney, and J. J. Burns, Protective effect of ascorbic acid on hepatotoxicity caused by sodium nitrite plus aminopyrine, Proc. Nat. Acad. Sci. USA 70(5):747 (1973).
M. Greenblatt, Ascorbic acid blocking of aminopyrine nitrosation in NZO/BL mice, J. Natl. Cancer Inst. 50:1055 (1973).
E. A. Walker, B. Pignatelli, and M. Castegnaro, Catalytic effect of p-nitrosophenol on the nitrosation of diethyl-amine, J. Agric. Food Chem. 27(2):393 (1979).
S. Singer, Kinetics and mechanism of aliphatic transnitrosation, J. Org. Chem. 43(24):4612 (1978).
W. J. Mergens, J. J. Kamm, H. L. Newmark, W. Fiddler, and J. Pensabene, Alpha-tocopherol: uses in preventing nitrosamine formation, in: “Environmental Aspects of N-Nitroso Compounds,” E. A. Walker, M. Castegnaro, L. Griciute, R. E. Lyle, eds., IARC Publication No. 19, Lyon (1978).
J. J. Kamm, T. Dashman, H. Newmark, and W. J. Mergens, Inhibition of amine-nitrite hepatotoxicity by alpha-tocopherol, Tox. and Appl. Pharm. 41:575 (1977).
B. Astill, Phenolic antioxidants and the inhibition of hepatotoxicity from dimethylnitrosamine found in situ in the rat stomach, Food Cosmet. Toxicol. 15:167 (1977).
J. S. Patton and M. C. Carey, Watching fat digestion, Science 204: 145 (1979).
W. Fiddler, J. Pensabene and A. Wasserman, The role of lean and adipose tissue on the formation of nitrosopyrrolidine in fried bacon, J. Food Sci. 59:1070 (1974).
W. J. Mergens and W. Fiddler, unpublished work (1979).
J. H. Weisburger, L. A. Cohen, and E. L. Wynder, On the Etiology and metabolic epidemiology of the main human cancers, in: “Origins of Human Cancer,” H. H. Hiatt, J. D. Watson, J. A. Winsten, eds., Cold Spring Harbor, New York (1977).
S. S. Mirvish, Blocking the formation of N-nitroso compounds with ascorbic acid in vitro and in vivo, Ann. NY Acad. Sci. 258:175 (1975).
S. R. Tannenbaum, D. Fett, V. R. Young, P. Land and W. R. Bruce, Nitrite and nitrate are formed by endogenous synthesis in the human intestine, Science 200: 1487 (1978).
T. Wang, T. Kakizoe, P. Dion, R. Furrer, A. J. Varghese, and W. R. Bruce, Volatile nitrosamines in normal human feces, Nature 276: 280 (1978).
D. Fine, An assessment of human exposure to N-nitroso compounds, in: “Environmental Aspects of N-Nitroso Compounds,” E. A. Walker, M. Castegnaro, L. Griciute, R. E. Lyle, eds., IARC Scientific Publication No. 19, Lyon (1978).
T. A. Gough, K. S. Webb, and R. F. Coleman, Occurrence of volatile nitrosamines, Nature 272: 162 (1978).
E. Boyland, E. Nice, and K. Williams, The catalysis of nitrosation by thiocyanate from saliva, Fd. Cosmet. Toxicol. 9:639 (1971).
L. K. Keefer and P. P. Roller, N-nitrosation by nitrite ion in neutral and basic medium, Science 18: 1245 (1973).
P. N. Magee, R. Montesano, and R. Preussmann, N-nitroso compounds and related carcinogens, in: “Chemical Carcinogens,” C. Searle, ed., ACS Monograph 173, (1976).
J. Sander, Nitrosaminsynthese durch bakterien, Hopper Seyler’s, Z. Physiol. Chem. 349:429 (1968).
P. Klubes and W. R. Jondurf, Dimethylnitrosamine formation from sodium nitrite and dimethylamine by bacterial flora of rat intestine, Chem. Path. Pharmac. 2:24 (1971).
P. Klubes, I. Cerna, A. D. Rabinowitz, and W. R. Jondurf, Factors affecting dimethylnitrosamine formation from simple precursors by rat intestinal bacteria, Fd. Cosmet. Toxicol. 10:757 (1972).
A. J. Varghese, P. C. Land, R. Furrer, and W. R. Bruce, Nonvolatile N-nitroso compounds in human feces, in: “Environmental Aspects of N-Nitroso Compounds,” E. A. Walker, M. Castegnaro, L. Griciute, R. E. Lyle, eds., IARC Scientific Publication No. 19, Lyon (1978).
W. R. Bruce, A. J. Varghese, S. Wang, and P. Dion, 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., University Park Press, Baltimore (1979).
V. G. Bowen and R. H. Kiebel, Effects of nitrite and ascorbate on botulinal toxin formation in weiners and bacon, Proc. Meat Industry Research Conf. pp. 63–68 (1974).
W. Fiddler, J. Pensabene, E. H. Piotrowski, J. G. Phillips, J. Keating, W. J. Mergens, and H. L. Newmark, Inhibition of formation of volatile nitrosamines in fried bacon by the use of cure-solubilized alpha-tocopherol, J. Agric. Food Chem. 26(3):653 (1978).
N. P. Sen, B. Donaldson, S. Seaman, J. R. Iyengar, and W. F. Miles, Inhibition of nitrosamine formation in fried bacon by propyl gallate and L-ascorbyl palmitate, J. Agric. Food Chem. 24:397 (1976).
C. L. Walters, M. W. Edwards, T. S. Elsey, and M. Martin, The effect of antioxidants on the production of volatile nitrosamines during the frying of bacon, Z. Lebensm. Unters.-Forsch. 162:377 (1976).
L. J. Rubin and K. R. Bharucha, Long chain acetals of ascorbic acid, Paper presented at the Expert Panel on Nitrite and Nitrosamines, Washington, D.C., August 17, 1977.
American Meat Institute in collaboration with Hoffmann-La Roche Inc., unpublished study (1978).
R. Bonnett, A. Charalambides, M. Hursthouse, K. Malik, P. Nicolaidou, and G. Sheldrick, The reaction of ethoxyquin (6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline) with nitrous acid, J. Chem. Soc. Perkin trans I 2:488 (1979).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1980 Springer Science+Business Media New York
About this chapter
Cite this chapter
Mergens, W.J., Newmark, H.L. (1980). Antioxidants as Blocking Agents Against Nitrosamine Formation. In: Simic, M.G., Karel, M. (eds) Autoxidation in Food and Biological Systems. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9351-2_21
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9351-2_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9353-6
Online ISBN: 978-1-4757-9351-2
eBook Packages: Springer Book Archive