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.
The questions of whether and how N-nitroso compounds (NOC) may be inducing cancer in humans are discussed. The principal subjects covered include nitrite-derived alkylating agents that are not NOC, reasons for the wide tissue specificity of carcinogenesis by NOC, the acute toxicity of nitrosamines in humans, mechanisms of in vivo formation of NOC by chemical and bacterial nitrosation in the stomach and via nitric oxide (NO) formation during inflammation, studies on nitrite esters, use of the nitrosoproline test to follow human gastric nitrosation, correlations of nitrate in food and water with in vivo nitrosation and the inhibition of gastric nitrosation by vitamin C and polyphenols. Evidence that specific cancers are caused by NOC is reviewed for cancer of the stomach, esophagus, nasopharynx, urinary bladder in bilharzia and colon. I review the occurrence of nitrosamines in tobacco products, nitrite-cured meat (which might be linked with childhood leukemia and brain cancer) and other foods, and in drugs and industrial situations. Finally, I discuss clues from mutations in ras and p53 genes in human tumors about whether NOC are etiologic agents and draw some general conclusions.
Mirvish
S S
SS
Eppley Institute for Research in Cancer, Department of Pharmaceutical Sciences, Omaha, NE, USA.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D064420:Drug-Related Side Effects and Adverse Reactions; D004781:Environmental Exposure; D004938:Esophageal Neoplasms / Q000139:chemically induced; D005506:Food Contamination; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced*; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000139:chemically induced; D009569:Nitric Oxide / Q000096:biosynthesis / Q000633:toxicity; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity; D015538:Nitrosation; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D012907:Smoking / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000139:chemically induced; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D009602:Nitrosamines; D009603:Nitroso Compounds; D009569:Nitric Oxide