任晓倩^1,2,
张海军^1,,,
耿柠波¹,
王菲迪³,
张保琴¹,
罗云^1,2,
陈吉平^1,,
1. 中国科学院大连化学物理研究所, 中国科学院分离分析化学重点实验室, 大连 116023;
2. 中国科学院大学, 北京 100049;
3. 浙江省农业科学院农产品质量标准研究所, 省部共建国家重点实验室培育基地-浙江省植物有害生物防控重点实验室, 杭州 310021

作者简介: 任晓倩(1991-),女,博士研究生,研究方向为环境毒理学,E-mail:renxiaoqian@dicp.ac.cn.

通讯作者: 张海军,hjzhang@dicp.ac.cn ; 陈吉平,chenjp@dicp.ac.cn

基金项目: 国家自然科学基金项目(21337002，21707140)


中图分类号: X171.5

Comparing the Disrupting Effects of Short-, Medium- and Long-Chain Chlorinated Paraffins on Human Hepatic Cell Metabolism

Ren Xiaoqian^1,2,
Zhang Haijun^1,,,
Geng Ningbo¹,
Wang Feidi³,
Zhang Baoqin¹,
Luo Yun^1,2,
Chen Jiping^1,,
1. CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;
2. University of Chinese Academy of Sciences, Beijing 100049, China;
3. State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Quality and Standard for Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China

Corresponding authors: Zhang Haijun,hjzhang@dicp.ac.cn ; Chen Jiping,chenjp@dicp.ac.cn

CLC number: X171.5

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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。
关键词: 氯化石蜡/
HepG2细胞/
代谢组学/
磷脂代谢/
脂肪酸代谢/
氨基酸代谢

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.
Key words:chlorinated paraffins/
HepG2 cell/
metabolomics/
phospholipid metabolism/
fatty acid metabolism/
amino acid metabolism.