Hemoglobin adducts as biomarkers of exposure to and metabolic activation of carcinogenic tobacco-specific nitrosamines.
The carcinogenic tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.
Hecht
S S
SS
American Health Foundation, Valhalla, New York 10595.
Carmella
S G
SG
Murphy
S E
SE
D000818:Animals; D015415:Biomarkers; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics; D004249:DNA Damage; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D009602:Nitrosamines / Q000378:metabolism* / Q000493:pharmacokinetics; D010947:Plants, Toxic; D051381:Rats; D014026:Nicotiana
D015415:Biomarkers; D002273:Carcinogens; D006454:Hemoglobins; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine