摘要:
短链氯化石蜡(short-chain chlorinated paraffins,SCCPs)是一组成分复杂的氯代正构烷烃,在环境中普遍存在。然而有关其毒性机理的信息十分有限,限制了对其健康风险的评估。本研究采用液相色谱-串联质谱(LC-MS/MS)分析技术,研究了不同剂量的SCCPs暴露(0、1.0、10.0和100.0μg·L-1;C13-CPs;55.0%Cl)对人体肝癌细胞Hep G2的糖代谢、氨基酸代谢和脂肪酸代谢的影响。通过偏最小二乘判别分析(PLS-DA)鉴别各组代谢产物谱差异,发现3个SCCPs暴露剂量组均能够与对照组完全分开,表明SCCPs短期暴露能够引起细胞代谢活动的显著改变。SCCPs的低剂量暴露可明显刺激Hep G2细胞对氨基酸的吸收。与对照组相比,SCCPs低剂量暴露组(1.0μg·L-1)培养基中谷氨酰胺、色氨酸和丝氨酸的含量显著(P<0.05)降低。而高剂量SCCPs(100.0μg·L-1)暴露抑制了细胞对氨基酸和葡萄糖吸收,但促进了乳酸、丙氨酸、半胱氨酸的生成。氨基酸吸收的抑制不可避免地会影响蛋白质的合成。同时,SCCPs的暴露使饱和脂肪酸代谢紊乱,使不饱和脂肪酸水平上调。为确定SCCPs的毒性作用方式,有必要从转录组和蛋白组层面进一步研究其毒性机制。
Abstract:
Short chain chlorinated paraffins(SCCPs,C10-13) are a large and complex group of polychlorinated n-alkanes,and ubiquitously found in the environment. However,very limited information is available for their toxicity mechanism,limiting the evaluation of their health risks. In this study,liquid chromatography-tandem mass spectrometry(LC-MS/MS) was adopted to investigate the influence of SCCPs exposure with different doses(0,1.0,10.0 and 100.0 μg·L-1; C13 -CPs; 55.0% Cl) on the metabolism of glucose,amino acids and fatty acids in human hepatoma Hep G2 cells. The result of partial least squares discriminant analysis(PLS-DA) showed that all SCCPs exposure groups were clearly distinct from the control group,indicating a significant metabolic perturbation inducedby SCCPs. Low-dose SCCPs exposure promoted the import of extracellular amino acids into cells. Compared with the control group,the contents of glutamine,tryptophan and serine in the culture medium of low-dose SCCPs exposure group(1.0 μg·L-1) were significantly decreased(P<0.05). However,the high-dose SCCPs exposure(100.0 μg·L-1) inhibited the transport of amino acids and glucose into cells,and significantly up-regulated the biosynthesis of lactic acid,alanine and cysteine. The disorder of amino acids metabolism would inevitably affect the protein biosynthesis. Meanwhile,SCCPs perturbed the metabolism of unsaturated fatty acids,and markedly up-regulated the contents of polyunsaturated fatty acids. In order to make sure the mode of action of SCCPs,transcriptomic and proteomic evidences on SCCPs toxicity should be further provided.