Ultrasensitive method for the determination of 4-hydroxy-1-(3-pyridyl)-1-butanone-releasing DNA adducts by gas chromatography-high resolution mass spectrometry in mucosal biopsies of the lower esophagus.
Anal Bioanal Chem
; 393(5): 1525-30, 2009 Mar.
Article
en En
| MEDLINE
| ID: mdl-19104779
ABSTRACT
4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts are formed by metabolic activation of the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). NNK and NNN are considered carcinogenic to humans by the International Agency for Research on Cancer. Existing analytical methods for determination of HPB-releasing DNA adducts require 0.3-2.0 g of human target tissues such as lung and esophagus. For adduct determination in milligram amounts of biopsy samples, an ultrasensitive and specific method is presented using capillary gas chromatography coupled to a high-resolution mass spectrometer operated in the negative chemical ionization mode (GC-NCI-HRMS). The method has a limit of detection of 4.6 fmol HPB, a limit of quantification of 14.9 fmol HBP and a recovery of 45 +/- 15%. Intra- and inter-day imprecision for N = 6 samples were calculated with coefficients of variation of <3.1%. Method applicability was evaluated with biopsies of esophageal mucosa (N = 14) yielding 5.6 +/- 1.9 mg tissue and a mean adduct level of 6.13 +/- 9.35 pmol HPB/mg DNA.
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MEDLINE
Asunto principal:
Piridinas
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Butanonas
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Aductos de ADN
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Esófago
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Cromatografía de Gases y Espectrometría de Masas
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Membrana Mucosa
Idioma:
En
Revista:
Anal Bioanal Chem
Año:
2009
Tipo del documento:
Article