Plasma metabonomics investigation reveals involvement of fatty acid oxidation in hematotoxicity in Chinese benzene-exposed workers with low white blood cell count.
Plasma metabonomics investigation reveals involvement of fatty acid oxidation in hematotoxicity in Chinese benzene-exposed workers with low white blood cell count.
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血浆代谢组学研究揭示脂肪酸氧化与白细胞计数低的中国接触苯工人的血液毒性有关。
DOI：
10.1007/s11356-018-3160-2
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Pu Yuepu
中科院分区：
文献类型：
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作者：
Sun Rongli;Xu Kai;Zhang Qiaoyun;Jiang Xiaoyun;Man Zhaodi;Yin Lihong;Zhang Juan;Pu Yuepu
苯是一种环境和职业污染物。职业性苯接触的健康危害是我国重要的公共卫生问题。本研究采用高效液相色谱-飞行时间质谱联用技术分析了低白色血细胞数苯暴露工人和健康对照者血浆中的代谢物。为了筛选潜在的苯血液毒性生物标志物和代谢途径，使用主成分分析来检查血浆样品中代谢物谱的变化。脂肪酸氧化（FAO）途径的改变与我们先前在小鼠模型中的发现一致;因此，选择两个关键基因并在WBC样品中验证。共鉴定出9种代谢产物在BLWs中发生了显著变化，它们分别参与谷胱甘肽代谢、卟啉代谢、脂质代谢途径和FAO代谢。与健康对照组相比，BLWs中肉毒碱酰基转移酶（CRAT）和ACADVL的mRNA表达显著增加。白细胞计数与AVADVL表达呈负相关。这些异常代谢产物可作为苯血液毒性的潜在生物标志物。此外，脂肪酸氧化途径可能在苯引起的血液毒性的发展中起关键作用。
Benzene is an environmental and occupational contaminant. Health hazards associated with occupational benzene exposure is a major public health problem in China. In this study, we analyzed metabolite profiles among plasma samples collected from benzene-exposed workers with low white blood cell count (BLWs) and healthy controls using high-performance liquid chromatography–time-of-flight mass spectrometry. To screen potential benzene hematotoxicity biomarkers and metabolic pathways, principal component analysis was used to examine metabolite profile changes in plasma samples. The alterations in fatty acid oxidation (FAO) pathway were consistent with our previous findings in a mouse model; hence, two key genes were selected and verified in WBC samples. A total of nine identified metabolites were significantly changed in BLWs, which were involved in glutathione metabolism, porphyrin metabolism, lipid metabolism pathway, and FAO metabolism. Furthermore, compared with healthy controls, the mRNA expressions of carnitine acyltransferase (CRAT) and ACADVL were significantly increased in BLWs. Particularly, WBC counts was negatively correlated with the expression of AVADVL in BLWs. These aberrant metabolites could act as potential biomarkers for benzene hematotoxicity. In addition, fatty acid oxidation pathway may play a critical role in the development of hematotoxicity caused by benzene.