Carcinogenicity and metabolic activation of tobacco-specific nitrosamines: current status and future prospects.

Over the past decade, research on the carcinogenicity and metabolism of tobacco-specific nitrosamines has provided a basis for understanding their possible roles in human cancer. 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone appears to be the most important tobacco-specific nitrosamine, because of its strong carcinogenicity. A large population of smokers and snuff dippers is exposed to significant quantities of this and the other tobacco-specific nitrosamines on a daily basis. Further research should now focus on the relationship between human exposure to tobacco-specific nitrosamines and the risk of developing tobacco-related cancers. Several important areas can be identified: we need to develop sensitive assays that can be used routinely to quantify the levels of tobacco-specific nitrosamines or their metabolites in human blood, and the levels of their DNA adducts in human tissues; we need to establish, through comparative metabolic and DNA-binding studies, the relationships between the organospecificity of tobacco-specific nitrosamines in experimental animals and that in humans; we may also be enabled to identify naturally-occurring substances that can inhibit carcinogenesis by tobacco-specific nitrosamines. These research approaches will hopefully lead to a reduction in the incidence of tobacco-related cancers.