Effect of gender and cigarette smoking on urinary excretion of etheno DNA adducts in humans measured by isotope dilution gas chromatography/mass spectrometry

Effect of gender and cigarette smoking on urinary excretion of etheno DNA adducts in humans measured by isotope dilution gas chromatography/mass spectrometry
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DOI:
10.1016/j.toxlet.2006.12.005
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发表时间:
2007-02-28
期刊:
影响因子:
3.5
通讯作者:
Kao, Chi-Fu
Kao, Chi-Fu
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Hauh-Jyun Candy;Kao, Chi-Fu

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内源性前致突变DNA加合物1,N-6-乙烯基腺嘌呤(1,N-6-ethenoadenine,1,N-6-ethenoadenine)和3,N-4-乙烯基胞嘧啶(3,N-4-ethenocytosine,3,N-4-ethenocytosine,3,N-4-ethenocytosine,3,N-4-ethenocytosine)的形成被认为是脂质过氧化反应的生物标志物。在易患癌症的组织中观察到高水平的β-Ade和β-Cyt,表明这些加合物在癌症风险评估中的有效性。生物体液中DNA碱基加合物的存在被认为主要来自碱基切除修复(BER)系统。本文建立了一种同时测定人尿中β-Ade和β-Cyt的气相色谱/质谱(GC/MS)分析方法。在调整肌酐浓度后,18名男性吸烟者的尿中β-Ade和β-Cyt排泄量远高于10名男性非吸烟者(β-Ade p = 0.003,β-Cyt p = 0.04)。此外,14名女性非吸烟者的β-Ade和β-Cyt排泄量远高于10名男性非吸烟者(β-Ade p = 0.002,β-Cyt p = 0.005)。这些结果表明,性别,以及吸烟,和排泄的eAde和cDNACyt之间的统计学显着的关联。此外,在这42名受试者中,尿液中的β-Ade排泄与β-Cyt排泄相关(R-2 = 0.6846,p < 0.0001)。测量尿eAde和尿Cyt排泄可为致癌和化学预防研究提供有效的非侵入性生物标志物。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Endogenous formation of the promutagenic DNA adducts 1,N-6-ethenoadenine (epsilon Ade) and 3,N-4-ethenocytosine (epsilon Cyt) has been considered as biomarkers originated from lipid peroxidation. Elevated levels of epsilon Ade and epsilon Cyt were observed in cancer-prone tissues, suggesting the validity of these adducts in cancer risk assessment. The presence of DNA base adducts in biological fluids is considered to derive primarily from base excision repair (BER) systems. In this study, a modified gas chromatography/rnass spectrometry (GC/MS) method is developed for simultaneous analysis of epsilon Ade and epsilon Cyt in human urine. After adjusting for creatinine concentration, urinary excretion of epsilon Ade, as well as epsilon Cyt, is much higher in 18 male smokers than in 10 male nonsmokers (p = 0.003 for epsilon Ade and p = 0.04 for epsilon Cyt). Furthermore, excretion of epsilon Ade and epsilon Cyt in 14 female nonsmokers is much higher than in 10 male nonsmokers (p = 0.002 for epsilon Ade and p = 0.005 for epsilon Cyt). These results suggest a statistically significant association between gender, as well as smoking, and excretion of eAde and epsilon Cyt. Moreover, urinary excretion of epsilon Ade in these 42 subjects correlates with that of epsilon Cyt (R-2 = 0.6846, p < 0.0001). Measurement of urinary eAde and epsilon Cyt excretion should provide valid noninvasive biomarkers for carcinogenesis and chemoprevention studies. (c) 2006 Elsevier Ireland Ltd. All rights reserved.