Repeated Measurements of Urinary Methylated/Oxidative DNA Lesions, Acute Toxicity, and Mutagenicity in Coke Oven Workers
Repeated Measurements of Urinary Methylated/Oxidative DNA Lesions, Acute Toxicity, and Mutagenicity in Coke Oven Workers
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DOI：
10.1158/1055-9965.epi-08-0721
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发表时间：
2008-12-01
影响因子：
3.8
通讯作者：
Hu, Chiung-Wen
中科院分区：
文献类型：
--
作者：
Chao, Mu-Rong;Wang, Chien-Jen;Hu, Chiung-Wen
我们对焦炉工人进行了一项重复测量队列研究，以评估传统暴露生物标志物尿 1-羟基芘 (1-OHP) 与尿 8-氧代-7,8-二氢-2'-脱氧鸟苷 (8-oxodG)、N7-甲基鸟嘌呤 (N7-MeG) 等一系列生物标志物、急性毒性和致突变性之间的关系。在整个工作周期（包括连续工作 6 天和休息 2 天）期间，从高暴露工人（顶部炉区）和低暴露工人（侧炉区）总共采集了 8 个点尿样本。我们的结果表明，与低暴露工人相比，高暴露工人尿中 1-OHP、8-oxodG 和 N7-MeG 水平显着升高。通过Microtox试验和Ames试验分别测定，高暴露工人的尿液急性毒性和致突变性也显着增加。多变量回归分析显示，尿8-oxodG、N7-MeG或急性毒性与1-OHP浓度显着相关。总体而言，本研究表明，接触焦炉排放物会增加氧化损伤的 DNA 产物和尿液的致突变性，并且首次发现这种接触会增加 DNA 甲基化和尿急性毒性。焦炉排放物中甲基化剂的潜在来源值得进一步调查。此外，通过重复测量，发现尿1-OHP的时程模式与8-oxodG和N7-MeG不同，并且具有急性毒性和致突变性。这一发现意味着，在职业健康调查中经常进行的单一测量在使用时应采取一定的预防措施，因为单一测量可能无法提供正确的感兴趣信息。 （癌症流行病学生物标志物，2008 年以前；17(12):3381-9）
We conducted a repeated-measures cohort study of coke oven workers to evaluate the relationships between the traditional exposure biomarker, urinary 1-hydroxypyrene (1-OHP), and a series of biomarkers, including urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), N7-methylguanine (N7-MeG), acute toxicity, and mutagenicity. A total of eight spot urine samples were collected from each high-exposed (at topside oven area) and low-exposed workers (at side oven area) during the whole working cycle, which consisted of 6 consecutive days of working followed by 2 days off. Our results showed that the high-exposed workers had significantly higher urinary levels of 1-OHP, 8-oxodG, and N7-MeG compared with the low-exposed workers. Acute toxicity and mutagenicity of urine were also found to be markedly increased in the high-exposed workers, as determined by Microtox assay and Ames test, respectively. Multivariate regressions analysis revealed that the urinary 8-oxodG, N7-MeG, or acute toxicity was significantly correlated with 1-OHP concentrations. Overall, the present study showed that exposure to coke oven emissions increased oxidatively damaged DNA products and mutagenicity of urine, and for the very first time, such exposure was also found to increase DNA methylation and urinary acute toxicity. The potential source of methylating agents in coke oven emissions warrants further investigation. Additionally, with repeated measurements, the pattern of time course for urinary 1-OHP was found to be different from those of 8-oxodG and N7-MeG, as well as acute toxicity and mutagenicity. This finding implies that the single measurement that was often conducted in occupational healthy investigations should be used with certain precautions, because single measurement may fail to provide the proper information of interest. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3381-9)