Mass spectrometric analysis of tobacco-specific nitrosamine-DNA adducts in smokers and nonsmokers
| Autor: | Stephen S. Hecht, Shobha A. Akerkar, Mark Kagan, Peter G. Foiles, Steven G. Carmella, Gary D. Stoner, James H. Resau |
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| Rok vydání: | 1991 |
| Předmět: |
Adult
Male Nitrosamines Adolescent Tritium Toxicology Mass spectrometry Gas Chromatography-Mass Spectrometry Adduct Mice chemistry.chemical_compound Animals Humans Organic chemistry Globin Aged Aged 80 and over Chromatography Chemical ionization Chemistry Hydrolysis Smoking DNA General Medicine Middle Aged Nitrosamine Female Gas chromatography Gas chromatography–mass spectrometry |
| Zdroj: | Chemical Research in Toxicology. 4:364-368 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx00021a017 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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