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Comparative analysis of urinary N7-(2-hydroxyethyl)guanine for ethylene oxide- and non-exposed workers
Authors:Huang Chih-Chun Jean  Wu Chia-Fang  Shih Wei-Chung  Chen Ming-Feng  Chen Chang-Yuh  Chien Yeh-Chung  Liou Saou-Hsing  Chiang Su-Yin  Wu Kuen-Yuh
Institution:a Department of Food Science, National Pingtung University of Science and Technology, 1 Shuefu Rd., Neipu, Pingtung 91201, Taiwan
b Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Rd., Zhunan Town, Miaoli County 35053, Taiwan
c Graduate Institute of Occupational Safety and Health and Department of Occupational Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
d Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, 17 Shiujou Rd., Taipei 10055, Taiwan
e Institute of Occupational Safety and Health, Council of Labor Affairs, Executive Yuan, 99, Lane 407, Hengke Rd., Sijhih City, Taipei County 22143, Taiwan
f Department of Industrial Safety and Health, Kungkuang University, 34 Chung-Chie Rd., Shalu Town, Taichung County 44302, Taiwan
g School of Chinese Medicine, China Medical University, Taichung, Taiwan
Abstract:Ethylene oxide (EO), a direct alkylating agent and a carcinogen, can attack the nucleophilic sites of DNA bases to form a variety of DNA adducts. The most abundant adduct, N7-(2-hydroxyethyl)guanine (N7-HEG), can be depurinated spontaneously or enzymatically from DNA backbone to form abasic sites. Molecular dosimetry of the excised N7-HEG in urine can serve as an EO exposure and potential risk-associated biomarker. This study was to analyze N7-HEG in urine collected from 89 EO-exposed and 48 nonexposed hospital workers and 20 exposed and 10 nonexposed factory workers by using our newly developed on-line solid-phase extraction isotope-dilution LC-MS/MS method. Statistical analysis of data shows that the exposed factory workers excreted significantly greater concentrations of N7-HEG than both the nonexposed factory workers and hospital workers. Multiple linear regression analysis reveals that the EO-exposed factory workers had a significantly greater post-shift urinary N7-HEG than their nonexposed coworkers and hospital workers. These results demonstrate that analysis of urinary N7-HEG can serve as a biomarker of EO exposure for future molecular epidemiology studies to better understand the role of the EO-induced DNA adduct formation in EO carcinogenicity and certainly for routine surveillance of occupational EO exposure for the study of potential health impacts on workers.
Keywords:Ethylene oxide  N7-(2-hydroxyethyl)guanine  Online solid-phase extraction  LC-MS/MS
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