Mass spectrometric analysis of tobacco-specific nitrosamine-DNA adducts in smokers and nonsmokers. Chem Res Toxicol 1991;4(3):364-8
Date
05/01/1991Pubmed ID
1912321DOI
10.1021/tx00021a017Scopus ID
2-s2.0-0025731616 (requires institutional sign-in at Scopus site) 129 CitationsAbstract
A gas chromatography, negative ion chemical ionization mass spectrometry (GC-NICI-MS) based assay for tobacco-specific nitrosamine adducts of DNA is described. The assay is based on the observation that acid hydrolysis of DNA from animals treated with tobacco-specific nitrosamines releases 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB). HPB and the internal standard [4,4-D2]HPB are derivatized with pentafluorobenzoyl chloride and the resulting HPB-pentafluorobenzoate is purified by high-performance liquid chromatography prior to GC-NICI-MS analysis. DNA from human peripheral lung and tracheobronchial tissue, collected at autopsy, was analyzed for acid-released HPB. The mean HPB level (fmol/mg of DNA) for peripheral lung DNA was 11 +/- 16 (SD, n = 9) for smokers and 0.9 +/- 2.3 (n = 8) for nonsmokers. Mean adduct levels in tracheobronchus were 16 +/- 18 (n = 4) for smokers and 0.9 +/- 1.7 (n = 4) for nonsmokers. These are the first measurements of tobacco-specific nitrosamine-DNA adducts in humans. Further studies comparing the levels of DNA and globin adducts will provide a better understanding of the metabolic activation of tobacco-specific nitrosamines in humans and may provide a more accurate indication of an individual's risk of developing tobacco-related cancer.
Author List
Foiles PG, Akerkar SA, Carmella SG, Kagan M, Stoner GD, Resau JH, Hecht SSMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Aged, 80 and over
Animals
Chromatography
DNA
Female
Gas Chromatography-Mass Spectrometry
Humans
Hydrolysis
Male
Mice
Middle Aged
Nitrosamines
Smoking
Tritium