Chromosomal damage and polymorphisms of metabolic genes among 1, 3-butadiene-exposed workers in a matched study in China
Chromosomal damage and polymorphisms of metabolic genes among 1, 3-butadiene-exposed workers in a matched study in China
复制标题
DOI：
10.1093/mutage/ger091
复制
发表时间：
2012-07-01
期刊：
影响因子：
2.7
通讯作者：
Cao, Jia
中科院分区：
文献类型：
--
作者：
Xiang, Menglong;Ao, Lin;Cao, Jia
1，3-丁二醇（BD）是啮齿类动物的高效致癌物，2008年被国际癌症研究机构列为人类致癌物。然而，其诱导遗传损伤的能力以及代谢多态性对人类遗传损伤的影响都是有争议的。本研究对中国某BD制品车间45对职业接触工人和某行政办公室及循环水车间45对对照工人进行了BD暴露、代谢基因多态性与染色体损伤的关系研究。通过个人采样和固定采样评估BD暴露。采用微核试验（CBMN）检测外周血淋巴细胞染色体损伤终点;采用聚合酶链反应（PCR）或PCR-限制性片段长度多态性分析（PCR-RFLP）检测BD暴露组代谢基因[细胞色素P450 2 E1（CYP 2 E1）、谷胱甘肽S转移酶（GST）和微粒体环氧化物水解酶（mEH）]的多态性。结果表明，暴露组的平均BD测量值显著高于对照组（分别为个人采样和固定采样）。接触BD的工人微核率增高（8.00 +/- 3.78 ppm对5.62 +/- 2.41 ppm）和核质桥（NPB）（2.58 +/- 2.79千分之一对1.13 +/- 1.34千分之一）和核分裂指数下降（2.20 +/- 0.14 vs. 2.35 +/- 0.27）。同时，携带CYP 2 E1 c1 c2/c2 c2和mEH中/高（I）/高（H）组的BD作业工人的NPB频率显著高于携带CYP 2 E1 c1 c1的工人[频率比（FR）= 2.60，95%可信区间（CI）1.72-3.93; P < 0.0001）或mEH低（S）组（FR = 2.06，95% CI% 1.17-3.62; P < 0.05）。我们的研究表明，CBMN细胞组检测中的MNi和NPB频率可能是人类BD暴露的潜在遗传毒性生物标志物。CYP 2 E1和mEH基因多态性也可能影响BD工人的染色体不稳定性。
1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified as a human carcinogen in 2008 by the International Agency for Research on Cancer. However, its ability to induce genetic damage and the influence of metabolic polymorphisms to such damage in humans are both controversial claims. This study was conducted to investigate the relationships between exposure to BD, the polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and circulatory water workshop in China. Exposure to BD was evaluated by personal sampling and stationary sampling. Different chromosomal damage endpoints in peripheral blood lymphocytes were determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay; polymorphisms of metabolic genes [cytochrome P450 2E1 (CYP2E1), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH)] in BD-exposed group were detected by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism analysis. The results show that the average BD measurements of the exposed group were significantly higher than those for the control group (a personal sampling and stationary sampling, respectively). The BD-exposed workers exhibited increased frequencies of micronuclei (MNi) (8.00 +/- 3.78 parts per thousand versus 5.62 +/- 2.41 parts per thousand) and nucleoplasmic bridges (NPBs) (2.58 +/- 2.79 parts per thousand versus 1.13 +/- 1.34 parts per thousand) and a decreased nuclear division index (2.20 +/- 0.14 versus 2.35 +/- 0.27) when compared subjects in the control group. Meanwhile, BD-exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group had a significantly higher NPB frequency than those carrying CYP2E1 c1c1 [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72-3.93; P < 0.0001) or the mEH low(S) group (FR = 2.06, 95% CI% 1.17-3.62; P < 0.05), respectively. Our study suggests that MNi and NPB frequency in CBMN cytome assay could be potential genotoxic biomarkers for BD exposure in humans. The polymorphism of CYP2E1 and mEH could also affect the chromosomal instability of BD workers.