Tobacco-specific nitrosamines--metabolism and biological monitoring of exposure to tobacco products.

Tobacco-specific nitrosamines are derived from nicotine and related tobacco alkaloids and can be detected in tobacco products as well as in mainstream and sidestream smoke. Two of them, N-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, are strong carcinogens in laboratory animals. Because of its organospecificity for the lung, the latter is considered to be a causative factor in tobacco-related human lung cancer. Upon metabolic activation both nitrosamines give rise to a common reactive intermediate binding to macromolecules such as DNA and haemoglobin and hydrolysing to 4-hydroxy-1-(3-pyridyl)-1-butanone. Because of easy access to large quantities of haemoglobin from blood samples, it is most suitable for biomonitoring human exposure to tobacco-specific nitrosamines. A highly sensitive analytical method for determination of femtogram amounts of 4-hydroxy-1-(3-pyridyl)-1-butanone provides an approach to assess individual exposure to active and passive smoking.