Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, PR China.
Ecotoxicol Environ Saf. 2021 Jan 1;207:111562. doi: 10.1016/j.ecoenv.2020.111562. Epub 2020 Nov 3.
Low benzene exposure leads to hematotoxicity, but we still lack sensitive early monitoring and early warning markers. Benzene is associated with inflammation, which is mainly mediated by cytokines network. However, until now few studies have conducted high-throughput detection of multi-cytokines to get a global view of cytokine changes and screen for markers of benzene-induced toxicity. We hypothesized that cytokine profiles mediate benzene-induced hematotoxicity.
228 subjects consisting of 114 low benzene exposed workers and 114 healthy controls were recruited at Research Center of Occupational Medicine, Peking University Third Hospital, Beijing. The serum concentrations of 27 cytokines were detected by cytokinomics array, urinary benzene series metabolites were measured by UPLC-MS/MS, and peripheral blood cell counts were observed by basic blood test.
Among 27 cytokines, IL-9 and MIP1-α were significantly lower, but IL-4, IL-10, IL-15, MCP-1, TNF-α and VEGF were significantly higher in benzene exposure group than controls. Urinary benzene metabolite S-phenylmercapturic acid (S-PMA) was significantly higher in benzene exposure group and had a negative linear relationship with WBC count. S-PMA was only significantly associated with IL-9, meanwhile IL-9, IL-15 and VEGF had a positive linear relationship with WBC count. The bootstrapping mediation models showed that the effect of S-PMA on WBC count was partially explained by IL-9 for 10.11%.
This study suggests that exposure to benzene was associated with alternation of blood cell count and cytokine profiles in workers exposed to low levels of benzene, especially decreases of WBC count and IL-9. We also found IL-9 partially mediated the effect of low benzene exposure on WBC count, which may be a potential and promising early monitoring and early warning marker of benzene hematotoxicity.
低浓度苯暴露可导致血液毒性,但我们仍缺乏敏感的早期监测和预警标志物。苯与炎症有关,炎症主要由细胞因子网络介导。然而,到目前为止,很少有研究进行高通量检测多种细胞因子,以全面了解细胞因子变化并筛选苯诱导毒性的标志物。我们假设细胞因子谱介导了苯诱导的血液毒性。
在北京大学第三医院职业医学研究中心招募了 228 名研究对象,包括 114 名低苯暴露工人和 114 名健康对照者。通过细胞因子组学阵列检测血清中 27 种细胞因子的浓度,通过 UPLC-MS/MS 检测尿中苯系列代谢产物,通过基础血常规观察外周血白细胞计数。
在 27 种细胞因子中,暴露组中 IL-9 和 MIP1-α 显著降低,而 IL-4、IL-10、IL-15、MCP-1、TNF-α和 VEGF 显著升高。暴露组尿中苯代谢物 S-苯巯基尿酸(S-PMA)显著升高,与白细胞计数呈负线性关系。S-PMA 仅与 IL-9 显著相关,同时 IL-9、IL-15 和 VEGF 与白细胞计数呈正线性关系。Bootstrapping 中介模型显示,S-PMA 对白细胞计数的影响部分通过 IL-9 解释了 10.11%。
本研究表明,低水平苯暴露与工人血液细胞计数和细胞因子谱的改变有关,尤其是白细胞计数和 IL-9 的降低。我们还发现,IL-9 部分介导了低水平苯暴露对白细胞计数的影响,这可能是苯血液毒性的一个有潜力和有前途的早期监测和预警标志物。