Hu Guiping, Wang Tianjing, Liu Jiaxing, Chen Zhangjian, Zhong Lijun, Yu Shanfa, Zhao Zuchang, Zhai Min, Jia Guang
Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China.
Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, China.
Toxicol Lett. 2017 Aug 5;277:76-83. doi: 10.1016/j.toxlet.2017.05.026. Epub 2017 Jun 6.
Cr(VI) is widely-recognized as occupational and environmental contaminant, but the precise underlying mechanisms of Cr(VI) induced carcinogenic toxicity remain to be elucidated. Among kinds of toxic mechanisms, alteration of protein profiling usually elaborate a key mechanism of Cr(VI) induced toxicity and carcinogenesis. Large-scale proteins changes can reflect the onset or progression of carcinogenic toxicity, and potential serum protein biomarkers of Cr(VI) exposure. To gain an insight into the serum proteins expression profiling in chromate workers and find potential novel serum proteins biomarkers of Cr(VI) exposure, 107 male participants from a chromate production plant were recruited into the study. Questionnaire was applied to collect personal information and occupational history. Chromium concentration in blood (CrB) was measured to evaluate the participants' internal exposure. Serum proteins profiling and bioinformatics analysis were performed to explore differentially expressed proteins, proteins-chemical interaction network, critical proteins nodes related to the signaling pathways among 16 controls and 25 exposure workers in the first stage. ELISA tests were applied to verify the critical interested proteins nodes in the remaining 41 exposure workers and 25 controls. The results showed that the CrB levels in the control group were significantly lower than that in the exposure group (P<0.05). 44 significantly differentially expressed serum proteins formed 16 significant signaling pathways and a complex proteins-chemical interaction network, which associated with the immune system and extracellular matrix organization. C reactive protein (CRP), sonic hedgehog protein (SHH) and calcium located at critical nodes in proteins-chemical interaction network. There was a significant negative correlation between serum CRP level and CrB (P<0.05), and a significant positive correlation between SHH concentrations and CrB (P<0.05), which indicated that CRP and SHH might be as the potential novel biomarkers of Cr(VI) exposure. Also, the current study preliminarily paved the way to further functional studies to understand the underlying mechanisms and novel serum biomarkers of Cr(VI) exposure.
六价铬被广泛认为是一种职业和环境污染物，但其诱导致癌毒性的确切潜在机制仍有待阐明。在各种毒性机制中，蛋白质谱的改变通常是六价铬诱导毒性和致癌作用的关键机制。大规模的蛋白质变化可以反映致癌毒性的发生或进展，以及六价铬暴露的潜在血清蛋白生物标志物。为了深入了解铬酸盐工人的血清蛋白表达谱，并寻找六价铬暴露的潜在新型血清蛋白生物标志物，本研究招募了一家铬酸盐生产厂的107名男性参与者。通过问卷调查收集个人信息和职业史。测量血铬浓度（CrB）以评估参与者的体内暴露情况。在第一阶段，对16名对照者和25名暴露工人进行血清蛋白谱分析和生物信息学分析，以探索差异表达蛋白、蛋白-化学相互作用网络以及与信号通路相关的关键蛋白节点。采用酶联免疫吸附测定（ELISA）试验对其余41名暴露工人和25名对照者中的关键感兴趣蛋白节点进行验证。结果显示，对照组的CrB水平显著低于暴露组（P<0.05）。44种显著差异表达的血清蛋白形成了16条显著的信号通路和一个复杂的蛋白-化学相互作用网络，这些与免疫系统和细胞外基质组织相关。C反应蛋白（CRP）、音猬因子（SHH）和钙位于蛋白-化学相互作用网络的关键节点。血清CRP水平与CrB之间存在显著负相关（P<0.05），SHH浓度与CrB之间存在显著正相关（P<0.05），这表明CRP和SHH可能是六价铬暴露的潜在新型生物标志物。此外，本研究初步为进一步的功能研究铺平了道路，以了解六价铬暴露的潜在机制和新型血清生物标志物。
