Measurement of urinary excretion of 5-hydroxymethyluracil in human by GC/NICI/MS: Correlation with cigarette smoking, urinary TBARS and etheno DNA adduct

被引:25
作者
Chen, HJC [1 ]
Wu, CF [1 ]
Huang, JL [1 ]
机构
[1] Natl Chung Cheng Univ, Dept Biochem & Chem, Chiayi 62142, Taiwan
关键词
cigarette smoking; 1; N-6-ethenoadenine; 5-hydroxymethyluracil; mass spectrometry; oxidative DNA damage; TBARS; urine;
D O I
10.1016/j.toxlet.2004.11.009
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
5-Hydroxymethyluracil (5-HMU) is derived from radiation in addition to endogenous oxidative DNA damage and it is one of the most abundant DNA adducts. Human 5-HMU-DNA-glycosylase has been shown to repair this lesion. Whether urinary levels of 5-HMU is a valid biomarker for oxidative DNA damage in vivo has been investigated. However, controversial results on its relation to cigarette smoking were reported. To facilitate analysis of urinary 5-HMU in epidemiological studies, a highly sensitive and specific assay based on stable isotope dilution gas chromatography/negative ion chemical ionization/mass spectrometry was developed. The limit of detection for N-1,N-3-bis(pentafluorobenzyl)-HMU is 10 fg (20 amol) (S/N= 4) injected on column and the limit of quantification in urine was 0.7 nM of 5-HMU. Using as little as 10 muL of human urine samples, levels of urinary 5-HMU in 21 healthy volunteers were accurately quantified. No correlation was observed between urinary 5-HMU levels and cigarette smoking. However, there was a statistically significant association between urinary levels of 5-HMU and thiobarbituric acid-reactive substances (r = 0.71, p = 0.0003). In addition, urinary 5-HMU levels also correlated with urinary levels of 1,N-6-ethenoadenine (r = 0.54, p = 0.01). These findings suggest that this assay should be valuable in assessing the role of urinary 5-HMU as a biomarker of oxidative DNA damage and repair. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:403 / 410
页数:8
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