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.
Richter
E
E
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München.
Schäffler
G
G
Malone
A
A
Schulze
J
J
D000470:Alkaloids / Q000737:chemistry; D000611:Aminobiphenyl Compounds / Q000097:blood; D000818:Animals; D001711:Biotransformation; D002074:Butanones / Q000097:blood; D002273:Carcinogens / Q000032:analysis / Q000493:pharmacokinetics; D004784:Environmental Monitoring; D006454:Hemoglobins; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009602:Nitrosamines / Q000032:analysis / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D010947:Plants, Toxic; D011725:Pyridines / Q000097:blood; D051381:Rats; D012680:Sensitivity and Specificity; D014026:Nicotiana / Q000737:chemistry*; D014028:Tobacco Smoke Pollution / Q000032:analysis*
D000470:Alkaloids; D000611:Aminobiphenyl Compounds; D002074:Butanones; D002273:Carcinogens; D006454:Hemoglobins; D009602:Nitrosamines; D011725:Pyridines; D014028:Tobacco Smoke Pollution; C006757:4-biphenylamine; C074143:4-hydoxy-1-(3-pyridyl)-1-butanone