N-nitroso compounds as a cause of human cancer

Simultaneous consideration of epidemiological and experimental findings leads to the conclusion that the tobacco-specific nitrosamines (TSNA) 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) probably cause oral and respiratory cancers in humans. The role of other N-nitroso compounds (NOC) in the etiology of human cancer may best be defined by the study of known human carcinogens, such as certain foods eaten exclusively by populations with exceptionally high incidences and mortality rates for certain cancers. The evidence that NOC may be responsible for these elevated rates is reviewed in relation to two such high-risk populations: (i) residents of Lin-xian county in northern China, who have a striking excess of cancer of the oesophagus, and (ii) Cantonese people who have high rates of nasopharyngeal carcinoma (NPC). More studies are needed to define clearly the relationship between various types of cancers and prenatal or lifetime exposures to passive smoking. If passive smoking is found to increase the risk of developing various childhood and adult cancers, the NOC in tobacco are likely to be among the relevant carcinogens. Carcinogenesis models for studying the effects of prenatal exposure to NNK and NNN and other NOC seem particularly promising for the study of low-dose effects and modifying factors.