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。
Short chain chlorinated paraffins (SCCPs, C10.13) are a large and complex group of polychlorinated n-al- kanes, 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 spec- trometry (LC-MS/MS) was adopted to investigate the influence of SCCPs exposure with different doses (0, 1.0, 10.0 and 100.0 μg.Ll; C13-CPs; 55.0% CI) on the metabolism of glucose, amino acids and fatty acids in human hepatoma HepG2 ceils. 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 in-duced by SCCPs. Low-dose SCCPs exposure promoted the import of extracellular amino acids into cells. Com- pared with the control group, the contents of glutamine, tryptophan and serine in the culture medium of low-dose SCCPs exposure group (1.0 p~g.L-1) were significantly decreased (P〈0.05). However, the high-dose SCCPs expo- sure (100.0 /.Lg-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-reg- ulated the contents of polyunsaturated fatty acids. In order to make sure the mode of action of SCCPs, transcrip- tomic and proteomic evidences on SCCPs toxicity should be further provided.