摘要:
氯化石蜡(chlorinated paraffins, CPs)在中国大量生产和使用，导致其在环境介质中的含量较高。采用拟靶向代谢组学技术，比较研究了短、中和长链氯化石蜡在人体内暴露水平下(100 μg·L-1)对HepG2细胞代谢的影响。结果表明，短、中和长链氯化石蜡暴露引起了HepG2细胞增殖活力的降低与代谢活动的显著变化。短链氯化石蜡(SCCPs)暴露对细胞代谢的影响强度略高于中链氯化石蜡(MCCPs)和长链氯化石蜡(LCCPs)。3种氯化石蜡均显著扰乱了脂质代谢，且影响程度相近。显著受影响的代谢通路包括：甘油磷脂代谢、亚油酸代谢、α-亚麻酸代谢、花生四烯酸代谢和鞘磷脂代谢。同时，3种氯化石蜡暴露也显著扰乱了甘氨酸、丝氨酸和苏氨酸代谢，缬氨酸、亮氨酸和异亮氨酸生物合成，牛磺酸和亚牛磺酸代谢；此外，LCCPs还扰乱了苯丙氨酸、酪氨酸和色氨酸生物合成通路。相比于SCCPs和MCCPs，LCCPs对氨基酸代谢表现出更强的干扰效应。
Abstract:
Chlorinated paraffins (CPs) is widely produced and used in China, resulting in a high pollution level of CPs in the environment. In this study, a pseudotargeted metabolomics approach was used to compare the effects of short-, medium- and long-chain chlorinated paraffins at human internal exposure level (100 μg·L-1) on the metabolism of human hepatoma HepG2 cells. The results showed that exposure to three kinds of CPs all induced the reduction in cell viability and the significant variation of cell metabolism, and the impact degree of SCCPs on overall metabolism was a little higher than those of MCCPs and LCCPs. Three kinds of CPs all significantly disturbed lipid metabolism and exhibited similar impact degree. The most relevant lipid metabolism disturbed by CPs included glycerophospholipid metabolic pathway, linoleic acid metabolic pathway, α-linolenic acid metabolic pathway, arachidonic acid metabolic pathway and sphingomyelin metabolic pathway. In addition, three kinds of CPs all remarkably affected the amino acid metabolism, including glycine, serine and threonine metabolic pathway, valine, leucine and isoleucine biosynthesis pathway, and taurine and hypotaurine metabolic pathway. LCCPs also disturbed phenylalanine, tyrosine and tryptophan biosynthesis pathway. Compared with SCCPs and MCCPs, LCCPs exhibited a stronger effect on amino acid metabolism.
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