Carcinogenic effects of N-nitroso compounds in the environment


Divya Jain
Priya Chaudhary
Nidhi Varshney
Pracheta Janmeda


N-nitroso compounds (NOC) are produced by the acid catalyzed reaction of nitrite with certain nitrogen compounds. The gastrointestinal tract (GI) is the main site for the formation of reactive nitrogen species (RNS). Bacteria present on the GI tract surface reduced the dietary nitrate or nitrite into Nitric oxide NO and other related compounds. The clinical sign of NOC carcinogenicity varies according to species, dose, and route of administration. Humans are exposed to preformed N-nitroso compounds and endogenous NOC via the environmental food chain. Several NOC are potential human carcinogens, including DENA and NDMA, but evidence from population studies is inconsistent.


How to Cite
Jain, D., Chaudhary, P., Varshney, N. ., & Janmeda, P. (2020). Carcinogenic effects of N-nitroso compounds in the environment. Environment Conservation Journal, 21(3), 25-41.


  1. Ahmed, M., Rauf, M., Mukhtar, Z. and Saeed, N. A. 2017. Excessive use of nitrogenous fertilizers: an unawareness causing serious threats to environment and human health. Environmental Science and Pollution Research, 24(35): 26983-26987.
  2. Alaba, P. A., Sani, Y. M., Olupinla, S. F., Daud, W. M. W., Mohammed, I. Y., Enweremadu, C. C. and Ayodele, O. O. 2017. Toward N-nitrosamines free water: Formation, prevention, and removal. Critical Reviews in Environmental Science and Technology, 47(24): 2448-2489.
  3. Atakisi, E. and Merhan, O. 2017. Nitric oxide synthase and nitric oxide involvement in different toxicities. IntechOpen.
  4. Bao, L., Li, S., Ma, R. and Bo, A. 2019. The mechanism of Dedu seven-ingredient pill with safflower in resisting liver cancer. International Journal of Clinical and Experimental Medicine, 12(6): 6979-6988.
  5. Barnes, J. M. and Magee, P. N. 1954. Some toxic properties of dimethylnitrosamine. British Journal of Industrial Medicine, 11: 167-174.
  6. Bartsch, H. and Montesano, R. 1984. Relevance of nitrosamine to human cancer. Carcinogenesis, 5(11): 1381-1393.
  7. Bingham, S. A., Pignatelli, B., Pollock, J. R., et al., 1996. Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer? Carcinogenesis, 17: 515-23.
  8. Boyland, E., Carter, R. L., Gorrod, J. W. and Roe, F. J. C. 1968. Carcinogenic properties of certain rubber additives. European Journal of Cancer, 4: 233-239.
  9. Bretschneider, K. and Matz J. 1973. Nitrosamine (NA) in der atmosphSxischen und in der Luft am Arbeitsplatz. Arch. Geschwulstforseh., 42: 36-41.
  10. Bruning-Fann, C. S. 1993. The effects of nitrate, nitrite and n-nitroso compounds on human health. Veterinary and Human Toxicology, 35(3): 237.
  11. Cammack, R., Joannou, C. L., Cui, X. Y., Martinez, C. T., Maraj, S. R. and Hughes, M. N. 1999. Nitrite and nitrosyl compounds in food preservation. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1411 (2-3): 475-488.
  12. Castonguay, A., Lin, D., Stoner, G. D., Radok, P., Furuya, K., Hecht, S. S., Schut, H. A. J. and Klaunig, J. E. 1983. Comparative carcinogenicity in A/J mice and metabolism by cultured mouse peripheral lung of N’-nitrosonornicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and their analogue. Cancer Research, 43: 1223-1229.
  13. Chatterjee, S. and Fisher, A. B. 2004. ROS to the rescue. American Journal of Physiology-Lung Cellular and Molecular Physiology, 287: 704–705.
  14. Chen, K., Pittman, R. N. and Popel, A. S. 2008. Nitric oxide in the vasculature: where does it come from and where does it go? A quantitative perspective. Antioxidants & Redox Signaling, 10(7): 1185-1198.
  15. Cross, A. J., Pollock, J. R. and Bingham, S. A. 2003. Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. Cancer Research, 63: 2358–60.
  16. Dar, K. K., Ali, S., Ejaz, M., Nasreen, S., Ashraf, N., Gillani, S. F., Shafi, N., Safeer, S., Khan, M. A., Andleeb, S. and Mughal, T. A. 2019. In vivo induction of hepatocellular carcinoma by diethylnitrosamine and pharmacological intervention in Balb C mice using Bergenia ciliate extracts. Brazilian Journal of Biology, 79(4): 629-638.
  17. Davis, F. and Martin, S. P. 1998. Epidemiology – incidence and survival in central nervous system neoplasia. In: Bigner DD, ed. Russell and Rubinstein’s Pathology of Tumors of the Nervous System, 6th edn, 1(1): 5–45.
  18. Deichmann, W. B. 1969. Toxicology of Drugs and Chemicals. New York, Academic Press, pp.388.
  19. Dietrich, M., Block, G., Pogoda, J. M., Buffler, P., Hecht, S. and Preston-Martin, S. 2005. A review: Dietary and endogenously formed N-nitroso compounds and risk of childhood brain tumors. Cancer Causes and Control, 16: 619–635.
  20. Druckrey, H. and Preussmann, R. 1962. Zur Entstehung carcinogene Nitrosamine an Beispiel des Tabakrauchs. Naturwissenschaften, 49: 498-501.
  21. Druckrey, H. 1973a. Chemical structure and action in transplacental carcinogenesis and teratogenesis, in L. Tomatis and U. Mohr (eds.), Transplacental Carcinogenesis, Lyon, International Agency for Research on Cancer, IARC Scientific Publications No. 4: 45-58.
  22. Druckrey, H. 1973b. Specific carcinogenic and teratogenic effects of "indirect" alkylating methyl and ethyl compounds, and their dependency on stages of oneogenic developments, Xenobiotica, 3: 271-303.
  23. Druckrey, H., Preussmann, R., Ivankovic, S. and Schmahl, D. 1967. Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. (Organotropic carcinogenic effects of 65 various N-nitroso-compounds on BD rats). Z Krebsforsch; 69: 103–201.
  24. Eisenbrand, G., Ungerer, O. and Preussmann, R. 1974. Rapid formation of carcinogenic N-nitrosamines by interaction of nitrite with fungicides derived from dithiocarbamic acid in vitro under simulated gastric conditions and in vivo in the rat stomach. Food and Cosmetics Toxicology, 12: 229-232.
  25. Elespuru, R. K. and Lijinsky, W. 1973. The formation of carcinogenic nitroso compounds from nitrite and some types of agricultural chemicals. Food and Cosmetics Toxicology, 11: 807-817.
  26. Ender, F., Havre, G., Helgebostad, A., Koppang, N., Madsen, R. and Ceh, L. 1964. Isolation and identification of a hepatotoxic factor in herring meal produced from sodium nitrite preserved herring. Naturwissenschaften, 51: 637-638.
  27. Fan, T. Y., Morrison, J., Rounbehler, D. P., Ross, R., Fine, D. H., Miles, W. and Sen, N. P. 1977. N Nitrosodiethanolamine in synthetic cutting fluids: A part-per-hundred impurity. Science, 196: 70-71.
  28. Ferronato, N. and Torretta, V. 2019. Waste mismanagement in developing countries: a review of global issues. International Journal of Environmental Research and Public Health, 16(6): 1060.
  29. Ferysiuk, K. and Wójciak, K. M. 2020. Reduction of nitrite in meat products through the application of various plant-based ingredients. Antioxidants (Basel), 9(8): 711.
  30. Fine, D. H., Lieb, D. and Gufeh, F. 1975. Principle of operation of the thermal energy analyser (TEA) for the trace analysis of volatile and non-volatile N-nitroso compounds. Journal of Chromatography, 107: 351-357.
  31. Fine, D. H., Rounbehler, D. P., Belcher, N. M. and Epstein, S. S. 1976. N-Nitroso compounds: Detection in ambient air. Science, 192: 1328-1330.
  32. Freund, H. A. 1937. Clinical manifestations and studies in parenchymatous hepatitis. Annals of Internal Medicine, 10: 1144–1155.
  33. Fridman, A. L., Mukhametschin, F. M. and Novikov, S. S. 1971. Advances in the chemistry of aliphatic N-nitrosamines. Russian Chemical Reviews, 40: 34-50.
  34. Goodman, M. T., Hankin, J. H., Wilkens, L. R. and Kolonel. L. N. 1992. High-fat foods and the risk of lung cancer. Epidemiology, Cambridge, MA, 3: 288-299.
  35. Hancock, J. T., Desikan, R. and Neill, S. J. 2001. Role of reactive oxygen species in cell signalling pathways. Biochemical Society Transactions, 29: 345–350.
  36. Hard, G. C. and Butler, W.H. 1970a. Cellular analysis of renal neoplasia: induction of renal tumours in dietary conditioned rats by dimethylnitrosamine, with a reappraisal of morphological characteristics. Cancer Research, 30: 2796-2805.
  37. Hard, G. C. and Butler, W. H. 1970b. Toxicity of dimethyinitrosamine for the rat testes. Journal of Pathology, 102: 201-207.
  38. Hassan, S. K., Mousa, A. M., EI-Sammad, N. M., Abdel-Halim, A. H., Khalil, W. K. B., Elsayed, E. A., Anwar, N., Linscheid, M. W., Moustafa, E. S., Hashim, A. N. and Nawwar, M. 2019. Toxicology Reports, 6: 1071-1085.
  39. Hoffman, D., Rathkamp, G. and Liu, Y. Y. 1974. Chemical studies on tobacco smoke. XXVI. On the isolation and identification of volatile and non-volatile N-nitrosamines and hydrazines in cigarette smoke, in P. Bogovski and E.A. Walker (eds.), N-Nitroso Compounds in the Environment, Lyon, International Agency for Research on Cancer, IARC Scientific Publications No. 9, 159-165.
  40. Hoffmann, D., Rivenson, A., Amin, S. and Hecht, S. S. 1984. Dose-response study of the carcinogenicity of tabacco-specific N-nitrosamines in F344 rats. Journal of Cancer Research and Clinical Oncology, 108: 81-86.
  41. Hughes, R., Cross, A. J., Pollock, J. R. and Bingham, S. 2001. Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation. Carcinogenesis, 22:199–202.
  42. IARC, 1974. N-Nitroso Compounds in the Environment. In Bogovski, P. and E.A. Walker (eds.), Lyon, International Agency for Research on Cancer (IARC) Scientific Publications No. 9.
  43. IARC, 1978. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some N-Nitroso Compounds. Lyon, France.
  44. Jain, D., Uniyal, N., Mitra, D. and Janmeda, P. 2020. Traditional resources and use of aromatic and ethnomedicinal plants in Uttarakhand: Compliment of nature. International Journal of Herbal Medicine, 8(5): 88-95.
  45. Janmeda, P., Sharma, V., Paliwal, R., Sharma, S., Singh, L., Savita, B. S., Yadav, S. and Sharma, S. H. 2011a. Chemoprotective activity of hydro-ethanolic extract of Euphorbia neriifolia Linn leaves against DENA-induced liver carcinogenesis in mice. Biology and Medicine, 3 (2) Special Issue: 36-44.
  46. Janmeda, P., Sharma, V., Singh, L., Paliwal, R., Sharma, S., Yadav, S. and Sharma, S. 2011b. Chemopreventive Effect of Hydroethanolic Extract of Euphorbia neriifolia Leaves Against DENA-Induced Renal Carcinogenesis in Mice. Asian Pacific Journal of Cancer Prevention, 12: 677-683.
  47. Kamangar, F., Chow, W. H., Abnet, C. and Dawsey, S. 2010. Environmental causes of esophageal cancer. Gastroenterology Clinics of North America, 38(1): 27-vii.
  48. Kleihues, P., Aguzzi, A. and Ohgaki, H. 1995. Genetic and environmental factors in the etiology of human brain tumors. Toxicology Letters, 82–83: 601–605.
  49. Kobayashi, J. 2018. Effect of diet and gut environment on the gastrointestinal formation of N-nitroso compounds: a review. Nitric Oxide, 73: 66-73.
  50. Lee, D. H. K. 1970. Nitrates, nitrites and methemoglobinemia. Environmental Research, 3: 484-451.
  51. Lijinsky, E. 1987. Structure-activity relations in carcinogenesis by N-nitroso compounds. Cancer and Metastasis Reviews, 6: 301-356.
  52. Lijinsky, W. and Epstein, S. S. 1970. Nitrosamines as environmental carcinogens. Nature, 225 (5227): 21–23.
  53. Lijinsky, W. and Taylor, H. W. 1976. Carcinogenicity test of two unsaturated derivatives of N-nitrosopiperidine in Sprague-Dawley rats. Journal of the National Cancer Institute, 57(6).
  54. Linjinsky, W. and Kovatch, R. M. 1988. Comparative carcinogenesis by Nitrosomethylalkylamines in Syrian Hamsters. Cancer Research, 48: 6648-6652.
  55. Loh, Y. H., Jakszyn, P., Luben, R. N., Mulligan, A. A., Mitrou, P. N., and Khaw K. T. 2011. N-nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk Study. American Journal of Clinical Nutrition, 93: 1053–61.
  56. Low, H. 1974. Nitroso Compounds. Archives of environmental health, 29: 256-260.
  57. Lundberg, J. O. and Weitzberg, E. 2013. Biology of nitrogen oxides in the gastrointestinal tract. Gut, 62(4): 616-629.
  58. Ma, L., Hu, L., Feng, X. and Wang, S. 2018. Nitrate and nitrite in health and disease. Aging and Disease, 9(5): 938-945.
  59. Maduagwu, E. and Bassir, O. 1980. A comparative assessment of toxic effects of dimethylnitrosamine in six different species. Toxicology and Applied Pharmacology, 53: 211-219.
  60. Magee, P. N. 1989. The experimental basis for the role of nitroso compounds in human cancer, In D. Forman and D. Shuker (Eds.), Nitrate, Nitrite, and Nitroso Compounds in Human Cancer. Journal of Cancer Survivorship, 8: 207-239.
  61. Magee, P. N. and Barnes, J. M. 1956. The production of malignant primary hepatic tumours in the rat by feeding dimethylnitrosamine. British Journal of Cancer, 10: 114–122.
  62. Magee, P. N. and Barnes, J. M. 1967. Carcinogenic nitroso compounds. Advances in Cancer Research, 10: 163-246.
  63. Magee, P. N. and Lee, K. Y. 1963. Experimental toxic liver injury by some nitrosamines. Annals of the New-york academy of sciences, 104: 916–925.
  64. Magee, P. N. 1972. Possibilities of hazard from nitrosarnines in industry. Annals of Occupational Hygiene, 15:19-22.
  65. Magee, P. N. 1987. Nitrosamines and human cancer: some implications of basic research In J. G. Cory et al. (eds.), Cancer Biology and Therapeutics, 183-195.
  66. Magee, P. N., Montesano, R. and Preussmann, R. 1976. In C. Searle (ed.), Chemical Carcinogens. American Chemical Society Monographs,173 in press.
  67. Martin, S. P., Yu, M. C., Benton, B. and Henderson, B. E. 1982. N-Nitroso compounds and childhood brain tumors: a case– control study. Cancer Research, 42: 5240–5245.
  68. McCormick, A., Nicholson, M. J., Baylis, M. A. and Underwood, J. G. 1973. Nitrosamines in cigarette smoke condensate, Nature (Lond.), 244: 237--238.
  69. Mirvish, S. S. 1975. Formation of N-nitroso compounds: chemistry, kinetics and in vivo occurrence. Toxicology and Applied Pharmacology, 31: 325--351.
  70. Mirvish, S. S. 1977. Nitroso compounds, nitrite, and nitrate: possible implications for the causation of human cancer. Proceedings of the Conference on Nitrogen as a Water Pollutant, 8 (4/5): 195-207.
  71. Mirvish, S. S. 1995. Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. Cancer Lett., 29: 93(1): 17-48.
  72. Mittal, G., Kaur, M. and Soni, G. 2002. Impact of hypercholesterolemia on in vitro toxicity of N-nitrosodiethylamine effect on lipid peroxidation of blood and tissue. Indian Journal of Experimental Biology, 40: 1071-1073.
  73. Monson, R. R. and MacMahon, B. 1984. Prenatal X-ray exposure and cancer in children. In: Boice Jr J.D, Fraumeni Jr JF, (eds.) Radiation Carcinogenesis: Epidemiology and Biological Significance, 97–105.
  74. Montesano, R. and Magee, P. N. 1970. Metabolism of dimethylnitrosamine by human liver slices in vitro. Nature (Lond.), 228: 173-174.
  75. Napalkov, N. P. 1974. Some general considerations on the problem of transplacental carcinogenesis, in L. Tomatis and U. Mohr (eds.), Transplacental Carcinogenesis, Lyon, International Agency for Research on Cancer, IARC Scientific Publications, No. 4, 1-13.
  76. Ohshima, H., Sawa, T. and Akaike, T. 2006. 8-Nitroguanine, a product of nitrative DNA damage caused by reactive nitrogen species: Formation, occurrence, and implications in inflammation and carcinogenesis. Antioxidants & Redox Signaling, 8: 1033–1045.
  77. Ozogul, Y. and Ozogul, F. 2019. Biogenic amines formation, toxicity, regulation in food, in Biogenic amines in food: analysis, occurrence and toxicity, 1-17.
  78. Philipps, W. E. J. 1971. Naturally occurring nitrate and nitrite in foods in relation to infant methaemoglobinaemia. Food and Cosmetics Toxicology, 9: 219-228.
  79. Pour, P., Gingell, R., Langenbach, R., et al., 1980. Carcinogenicity of N-nitrosomethyl (2-oxopropyl) amine in syrian hamsters. Cancer Research, 40(10): 3585-3590.
  80. Pour, P. M. 1983. Prostatic cancer induced in MRC rats by N-nitrosobis (2-oxopropyl)-amine and N-nitrosobis (2-hydroxypropyl amine). Carcinogenesis, 4(1): 49-55.
  81. Pracheta, Sharma, V., Paliwal, R., Sharma, S., Singh, L., Janmeda, BS., Yadav, S., Sharma SH. 2011. Chemo-protective activity of hydro-ethanolic extract of Euphorbia neriifolia Linn leaves against DENA-induced liver carcinogenesis in mice. Biology and Medicine, 3(2) Special Issue: 36-44.
  82. Prakash, A., Jain, D., Tripathi, R. and Janmeda, P. 2019. Pharmacognostical analysis of different parts of Cyperus rotundus L. Plant Science Today, 6: 607-612.
  83. Preussmann, R. and Stewart, B. W. 1984. N-Nitroso carcinogens, in: E. Searle (Ed.), Chemical Carcinogens. American Chemical Society Monographs, 182, American Chemical Society, Washington, DC, pp. 643-828.
  84. Preussmann, R., 1984. Carcinogenic N-Nitroso Compounds and Their Environmental Significance. Naturwissenschaften, 71: 25-30.
  85. Pruckrey, H., et al., 1964. Erzeugung von Krebs durch eine einmalige Dosis van MethylnitrosoHarnstoffund verschiedenen Dialkylnitrosaminen an Ratten. Z Krebsforsch, 66: 1-10.
  86. Razzak, K. S. B., Jain, D., Hossain, M. N., and Bushra, A., 2020. Plant edible vaccines: a natural way of vaccination. Vigyan Varta, 1: 21-24.
  87. Rhoades, J. W. and Johnson D. E. 1972. N-Dimethylnitrosamine in tobacco smoke condensate. Nature (Lond.), 236: 307-308.
  88. Rimm, I. J., Li, F. C., Tarbell, N. J., Winston, K. R. and Sallan, S. E. 1987. Brain tumors after cranial irradiation for childhood acute lymphoblastic leukemia. A 13-year experience from the Dana-Farber Cancer Institute and the Children’s Hospital. Cancer, 59: 1506–1508.
  89. Rivenson, A., Hoffman, D., Prokopczyk, B., et al., 1988. Induction of lung and exocrine pancreas tumors in F344 rats by tobacco-specific and areca-derived-N-nitrosamines. Cancer Research, 48: 6912-6917.
  90. Rodvall, Y., Pershagen, G., Hrubec, Z., Ahlborn, A., Pedersen, N. L. and Boice, J. D. 1990. Prenatal X-ray exposure and childhood cancer in Swedish twins. International Journal of Cancer, 46: 362–365.
  91. Rostkowska, K., Zwierz, K., Rozanski, A., Moniuszko, J. J. and Roszczenko, A. 1998. Formation and metabolism of N-nitrosamine. Polish Journal of Environmental Studies, 7: 321-325.
  92. Sakshaug, J., Sognen, E., Hansen, M. A. and Koppang, N. 1965. Dimethylnitrosamine; its hepatotoxic effect in sheep and its occurrence in toxic batches of herring meal. Nature (Lond.) 206: 1261-1262.
  93. Sander, J. 1967. Kann Nitrit in der menschlichen Nahrung Ursache einer Krebsentstehung durch Nitrosaminbildung sein?. Archives of Hygiene Sciences, 151: 22-28.
  94. Scanlan, R. A. 1975. N-Nitrosamines in foods. Critical Reviews in Food Science and Nutrition, 5: 357-402.
  95. Schildt, E. B., Eriksson, M., Hardell, L. and Magnuson, A. 1998. Oral snuff, smoking habits and alcohol consumption in relation to oral cancer in a Swedish case-control study. International Journal of Cancer, 77: 341-346.
  96. Schmähl, D. and Habs, M. 1980. Carcinogenicity of N-nitroso compounds. Oncology, 37: 237-242.
  97. Schmahl, D., Preussmann, R. and Hamper, H. 1960. Leberkrebserzeugende Wirkung von Diathylnitrosamin nach oraler Gabe bei Ratten. Naturwissenschaften, 47: 89.
  98. Sen, N. P., Donaldson, B. A. and Charbonneau, C. 1974. Formation of nitrosodimethylamine from the interaction of certain pesticides and nitrite, In P. Bogovski and E.A. Walker (eds.), N-Nitroso Compounds in the Environment, Lyon, International Agency for Research on Cancer, IARC Scientific Publications No. 9: 75-79.
  99. Shacter, E. and Weitzman, S. A. 2002. Chronic inflammation and cancer. Oncology (Huntington) 16: 217-32.
  100. Shaik, K. M., Sarmah, B., Wadekar, G. S. and Kumar, P. 2020. Regulatory Updates and Analytical Methodologies for Nitrosamine Impurities Detection in Sartans, Ranitidine, Nizatidine, and Metformin along with Sample Preparation Techniques. Critical Reviews in Analytical Chemistry, 1-19.
  101. Shapiro, S., Mealey, J. Jr. and Sartorius, C. 1989. Radiation-induced intracranial malignant gliomas. Journal of Neurosurgery, 71: 77–82.
  102. Sharma, V. and Janmeda, P. 2013. Chemopreventive role of Euphorbia neriifolia (linn) and its isolated flavonoid against n-nitrosodiethylamine-induced renal histopathological damage in male mice. Toxicology International, 20 (1): 101-7.
  103. Sharma, V. and Janmeda, P. 2019. Curative effect of isolated flavonoid and Euphorbia neriifolia extract on hepatocarcinoma induced by N-Nitrosodiethylamine in albino mice. Biochemical Cellular Archives, 19(2): 3205-3211.
  104. Sharma, V., Janmeda, P. 2014. Protective assessment of Euphorbia neriifolia and its isolated flavonoid against N-Nitrosodiethylamine-induced hepatic carcinogenesis in male mice: a histopathological analysis. Toxicology International, 21(1): 56-62.
  105. Sharma, V., Janmeda, P. and Singh, L. 2012. N-nitrosodiethylamine and carcinogenicity: An over review. International, Journal for Environmental Rehabilitation and Conservation, 3 (1): 56-67.
  106. Sharma, V., Janmeda, P., Paliwal, R., and Sharma, SH. 2012. Antihepatotoxic activity of Euphorbia neriifolia on xenobiotic enzymes and biochemical status against N-Nitrosodiethylamine induced-hepatocarcinogenesis in mice. Journal of Chinese Integrative Medicine, 10(11): 1303-1309.
  107. Silvester, K. R., Bingham, S. A., Pollock, J. R., Cummings, J. H. and Neill I. K. O. 1997. Effect of meat and resistant starch on fecal excretion of apparent N-nitroso compounds and ammonia from the human large bowel. Nutrition and Cancer, 29: 13–23.
  108. Singh, R., Kumar, N., Saminathan, M., Singh, K. P., Dhama, K., Milton, A. P. and Kurade, N. P. 2020. Therapeutic effect of hydroethanolic extract of Trianthema portulacastrum L. against N-Nitroso-N-Methylurea-induced mammary tumors in wistar rats. Indian Journal of Traditional Knowledge.
  109. Song, P., Wu, L. and Guan, W. 2015. Dietary nitrates, nitrites, and nitrosamine intake and the risk of gastric cancer: a meta-analysis. Nutrition, 7: 9872-9895.
  110. Stefani, E. D., Deneo-Pellegrini, H., Carzoglio, J. C., Ronco, A. and Mendilaharsu, M. 1996. Dietary Nitrosodimethylamine and the Risk of Lung Cancer: A Case-Control Study from Uruguay. Cancer Epidemiology, Biomarkers & Prevention, 5. 679- 682.
  111. Stoner, G. D. and Shimkin, M. B. 1982. Strain a mouse lung tumor bioassay. International Journal of Toxicology,
  112. Svoboda, D. and Reddy J. 1975. Some effects of chemical carcinogens on cell organelles, in F.F. Becket (ed.), Cancer, I, Plenum Press, New York and London.
  113. Szabo, C. and Ohshima, H. 1997. DNA damage induced by peroxynitrite: subsequent biological effects. Nitric Oxide, 1:373–385.
  114. Terasaki, Y., Akuta, T., Terasaki, M., Sawa, T., Mori, T., Okamoto, T., Ozaki, M., Takeya, M. and Akaike, T. 2006. Guanine nitration in idiopathic pulmonary fibrosis and its implication for carcinogenesis. American Journal of Respiratory and Critical Care Medicine, 174:665–673.
  115. Tiso, M. and Schechter, A. N. 2015. Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions. PLOS One, 10(3): e0119712.
  116. Tolba, R., Kraus, T., Liedtke, C., Schwarz, M. and Weiskirchen, R. 2015. Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice. Laboratory Animals, 49(S1) 59–69.
  117. Tomatis, L. 1974. Role of prenatal events in determining cancer risks, in E. Boyland and R. Goulding (eds.), Modern Trends in Toxicology, Butterworths, London, 163-178.
  118. Tricker, A. R., Kubacki, S. J. 1992. Review of the occurrence and formation of non-volatile N-nitroso compounds in foods. Food Additives & Contaminants, 9: 39–69.
  119. Tsubura, A., Lai, Y. C., Miki, H., Sasaki, T., Uehara, N., Yuri, T. and Yoshizawa, K. 2010. Animal models of N-methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trial. International Journal of Experimental and Clinical Pathophysiology and Drug Research, 25(1): 11-22.
  120. Upreti, S., Rajendra, S. V., Das, K. and Aryal, A. 2018. Antineoplastic Approach of Semecarpus anacardium Leaves Against N-Nitroso Diethylamine Initiated Hepatocellular Carcinoma. Indian Journal of Pharmaceutical Education and Research, 52(4):610-7.
  121. Verma, D., Mudgal, B., Chaudhary, P., Mahakur, B., Mitra, D., Pant, K., Mohapatra, P. K. D., Thapliyal, A. and Janmeda, P. 2020. Medicinal plant of Uttarakhand (India) and their benefits in the treatment of tuberculosis: current perspectives. Global Journal of Bio-Science and Biotechnology, 9(3): 75-85.
  122. Vlachou, C., Hofstädter, D., Rauscher-Gabernig, E., Griesbacher, A., Fuchs, K. and König, J. 2020. Probabilistic risk assessment of nitrates for Austrian adults and estimation of the magnitude of their conversion into nitrites. Food and Chemical Toxicology, 145: 111719.
  123. West, R. 2017. Tobacco smoking: Health impact, prevalence, correlates and interventions. Psychology & Health, 32(8): 1018–1036.
  124. WHO, 1971. International standards for drinking water. Third ed, Geneva, World Health Organization, 70.
  125. WHO, 1978. Nitrates, Nitrites, and N-nitroso compounds. Geneva, World Health Organization, 11-85.
  126. Winter, J. W., Paterson, S., Scobie, G., Wirz, A., Preston, T. and McColl K. 2007. N-nitrosamine generation from ingested nitrate via nitric oxide in subjects with and without gastroesophageal reflux. Gastroenterology, 133: 164-174.
  127. Yeh, T. S., Liao, S. F., Kuo, C. Y. and Hwang, W. I. 2013. Investigation of the nitrate and nitrite contents in milk and milk powder in Taiwan. Journal of Food and Drug Analysis, 21(1): 73-79.
  128. Zak, F. G., Holzner, J. H., Singer, E. J. and Popper, H. 1960. Renal and pulmonary tumors in rats fed dimethylnitrosamine. Cancer Research, 20: 96 -99.
  129. Zalatnai, A. and Schally, A. V. 1989. Treatment of N-Nitrosobis (2-oxopropyl) amine-induced pancreatic cancer in Syrian golden hamsters with D-Trp-6-LH-RH and somatostatin analogue RC-160 microcapsules. Cancer Research, 49(7).
  130. Zingue, S., Njuh, A. N., Tueche, A. B., Tamsa, J., Tchoupang, E. N., Kakene, S. D., Sipping, M. T. K. and Njamen, D. 2018. In vitro cytotoxicity and In vivo antimammary tumor effects of the hydroethanolic extract of Acacia seyal (Mimosaceae) stem bark. BioMed Research International,