Wang F P, Zhu X N, Zhang Z B, Chen L P, Fan J L, Li Q Y, Chen S, Chen W
Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, Guangzhou 510080, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2017 May 6;51(5):421-426. doi: 10.3760/cma.j.issn.0253-9624.2017.05.010.
To investigate the effect of polycyclic aromatic hydrocarbons (PAHs) exposure on the level of histone H3Ser10 phosphorylation (p-H3S10) and DNA damage degree in peripheral blood lymphocyte (PBLCs). 75 coke oven workers from Benxi steel plant in Liaoning Province of China (PAHs-exposed group) and local 50 hot rolling workers (control group) were recruited in this study with age, working years, labor intensity and high temperature for matching factors using cluster sampling method in 2014. HPLC-fluorescence was performed to determine the level of urinary 1-hydroxypyrene (1-OHP), DNA damage and specific histone modification were measured in PBLCs of the subjects through comet assay and ELISA assay, respectively. Linear regression model analysis was used to analyze the differences among PAHs exposure, DNA damage and p-H3S10 level in two groups. The Mediation analysis was used to analyze the regulated relationships between urinary 1-OHP, DNA damage and histone modification through the bootstrap method. Age of the control and the exposed group were (45.32±8.32) and (43.87±5.67) years old (0.284). The concentration of urinary 1-OHP, OTM value, Tail DNA% and p-H3S10 level in exposure group were higher than that in control group, while the ((5)-(95)) of p-H3S10 levels in control and exposed group were 2.21 (0.68-4.71), 4.54 (1.85-23.91) (0.001). The degree p-H3S10 level was increased after the subgroups which were (2.59±1.19)%, (3.24±2.81)%, (5.55±3.25)%, (8.77±7.84)%, respectively, divided by quantitated 1-OHP concentration as (0)-(25), (26)-(50), (51)-(75) and (76)-(100) (0.001). We also found the correlations between urinary 1-OHP and p-H3S10 level or OTM value or Tail DNA%, β (95%) were 0.264 (0.167-0.360), 0.500 (0.299-0.702), and 0.510 (0.384-0.671), respectively (0.001). Similar result was also observed between p-H3S10 level and OTM value or Tail DNA%, β (95%) were 0.149 (0.073-0.226) and 0.220 (0.132-0.308) (0.001). Moreover, the mediation effect value of DNA damage on PAHs induced p-H3S10 alteration was 0.054(0.040). The results suggested that PAHs exposure could induce DNA damage and an increase in histone H3Ser10 phosphorylation in PBLCs. Particularly, the alteration of H3S10 phosphorylation may play an important role in regulating cell DNA damage repair.
探讨多环芳烃（PAHs）暴露对人外周血淋巴细胞（PBLCs）组蛋白H3丝氨酸10磷酸化（p-H3S10）水平及DNA损伤程度的影响。2014年采用整群抽样方法，选取辽宁省本溪钢铁厂75名焦炉工人（PAHs暴露组）和当地50名热轧工人（对照组），以年龄、工龄、劳动强度和高温作为匹配因素。采用高效液相色谱-荧光法检测尿中1-羟基芘（1-OHP）水平，分别通过彗星试验和酶联免疫吸附测定法检测受试者PBLCs中的DNA损伤及特异性组蛋白修饰。采用线性回归模型分析两组PAHs暴露、DNA损伤和p-H3S10水平的差异。采用中介分析通过自抽样法分析尿1-OHP、DNA损伤和组蛋白修饰之间的调控关系。对照组和暴露组年龄分别为（45.32±8.32）岁和（43.87±5.67）岁（P=0.284）。暴露组尿1-OHP浓度、OTM值、尾DNA%和p-H3S10水平均高于对照组，对照组和暴露组p-H3S10水平的（（5）-（95））分别为2.21（0.68-4.71）、4.54（1.85-23.91）（P=0.001）。根据尿1-OHP浓度分为（0）-（25）、（26）-（50）、（51）-（75）和（76）-（100）亚组后，p-H3S10水平升高程度分别为（2.59±1.19）%、（3.24±2.81）%、（5.55±3.25）%、（8.77±7.84）%（P=0.001）。还发现尿1-OHP与p-H3S10水平、OTM值或尾DNA%之间存在相关性，β（95%）分别为0.264（0.167-0.360）、0.500（0.299-0.702）和0.510（0.384-0.671）（P=0.001）。p-H3S10水平与OTM值或尾DNA%之间也观察到类似结果，β（95%）分别为0.149（0.073-0.226）和0.2（0.132-0.308）（P=0.001）。此外，DNA损伤对PAHs诱导的p-H3S10改变的中介效应值为0.054（0.040）。结果表明，PAHs暴露可诱导PBLCs的DNA损伤及组蛋白H3丝氨酸10磷酸化增加。特别是，H3S10磷酸化的改变可能在调节细胞DNA损伤修复中起重要作用。
