Mass spectrometric analysis of tobacco-specific nitrosamine hemoglobin adducts in snuff dippers, smokers, and nonsmokers.
Hemoglobin adducts of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1(3-pyridyl)-1-butanone and N'-nitrosonornicotine were quantified in blood samples collected from snuff dippers, smokers, and nonsmokers. Mild base treatment of hemoglobin adducted by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or N'-nitrosonornicotine releases 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB). HPB was enriched by solvent partitioning and derivatized to its pentafluorobenzoate. After purification by high performance liquid chromatography, HPB-pentafluorobenzoate was analyzed by capillary column gas chromatography with detection by negative ion chemical ionization mass spectrometry and selected ion monitoring. [4,4-D2]HPB was used as internal standard. The detection limit for HPB-pentafluorobenzoate was approximately 100 amol/injection or 5 fmol/g hemoglobin. Mean adduct levels (fmol HPB/g hemoglobin) were 517 +/- 538 (SD) in snuff dippers, 79.6 +/- 189 in smokers, and 29.3 +/- 25.9 in nonsmokers. Adduct levels in snuff dippers and in a subgroup of smokers were higher than would have been predicted solely based on estimates of exposure to tobacco-specific nitrosamines. The results of this study provide the first measurements of tobacco-specific nitrosamine hemoglobin adducts in humans and suggest new approaches to understanding the metabolic activation of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine in humans.
Carmella
S G
SG
American Health Foundation, Valhalla, New York 10595.
Kagan
S S
SS
Kagan
M
M
Foiles
P G
PG
Palladino
G
G
Quart
A M
AM
Quart
E
E
Hecht
S S
SS
D000328:Adult; D002273:Carcinogens / Q000032:analysis*; D003367:Cotinine / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009602:Nitrosamines / Q000032:analysis*; D010947:Plants, Toxic; D012907:Smoking / Q000097:blood*; D014026:Nicotiana; D014030:Tobacco, Smokeless
D002273:Carcinogens; D006454:Hemoglobins; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D003367:Cotinine; C008655:N'-nitrosonornicotine