To investigate the mechanisms underlying metabolic toxicity and hepatotoxicity of dioxins,HepG2 cells were selected to be exposed to the most toxic dioxin,23,7,8-tetrachlorodibenz0-p-dioxin (TCDD) for 24 h,and the proliferative activity of HepG2 cells was determined by MTT assay,while low-molecular metabolites (amino acids,glucose,itrea and glycerol) were qualitatively and quantitatively analyzed by HPLC-MS/MS.Results showed that short-term TCDD exposure had little effect on the proliferative activity of HepG2 cells.Glucose consumption did not change significantly after 24 h-exposure to TCDD,but only when the concentration of TCDD increased to 1 nmol·L-1,glucose consumption showed a slight decrease.0.01 nmol·L-1 TCDD inhibited the synthesis of praline and glutamate in HepG2 cells,and the synthesis of glutamate decreased in an obvious dose-response manner.The absorbability of several amino acids (valine,tryptophan,tyrosine,methi-onine,leucine and isoleucine) was stimulated by TCDD in a dose-response manner.The productions of urea and glycerol tended to decrease with increasing TCDD concentration.After 24 h-exposure to 1 nmol·L-1TCDD,the productions of urea and glycerol decreased to 1% and 18% of that of the control group.These results demonstrated that short-term exposure to TCDD could affect low-molecular metabolites in HepG2 cells to different degrees.TCDD exerted toxicity to HepG2 cells by disturbing its metabolism.%为了研究二恶英对细胞的代谢毒性,探究其肝毒性的作用机制,以二恶英中毒性最强的2,3,7,8-四氯代二苯并-对-二恶英(TCDD)为代表污染物,以HepG2肝癌细胞为受试对象,采用四甲基偶氮唑蓝(MTT)法和高技液相色谱/串联质谱法考察了TCDD的24 h暴露对HepG2细胞的增殖活性以及细胞的葡萄糖、氨基酸、尿素和甘油等小分子代谢物的影响.结果显示,短暂的TCDD暴露对HepG2细胞的增殖活性无显著影响.24 h的TCDD暴露对细胞的葡萄糖消耗量无显著影响,但当TCDD浓度增至1 nmo1·L-1时,葡萄糖的消耗量表现出一定的降低趋势.0.01 nmol·L-1TCDD就会使细胞脯氨酸和谷氨酸的合成能力下降,且谷氨酸的变化表现出明显的剂量-效应关系；TCDD可刺激细胞对缬氨酸、苏氨酸、酪氨酸、甲硫氨酸以及亮氨酸与异亮氮酸的吸收,并具有明显的浓度依赖性.随着TCDD浓度的增加,甘油和尿素产生量的降低趋势逐渐明显,1 nmol· L-1TCDD处理24 h后,甘油和尿素的产生量仅为对照组的1％和18％.研究表明,TCDD在短时间内使HepG2细胞内的一系列小分子代谢产物发生了不同程度的改变,且呈现出一定的剂量-效应关系.可见,TCDD可通过干扰HepG2肝癌细胞的代谢过程产生毒性.
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