PCB77和Cd共同暴露诱导的线粒体损伤及其介导的联合毒性效应

Mitochondrial injury-regulated joint toxicity induced by combined exposure of PCB77 and Cd

本文以人肝癌细胞系SMMC-7721为生物模型,研究并比较了PCB77和Cd^(2+)对SMMC-7721细胞的单一与联合毒性.通过细胞活性检测发现,当Cd^(2+)暴露浓度为20μmol·L-1,PCB77暴露浓度为25μmol·L^(-1),暴露时间为48 h时,两种污染物产生明显的联合毒性.二者共同暴露虽然不影响细胞膜的完整性,但引起了线粒体膜电位下降、膜通透性显著增加,进而诱导细胞凋亡,同时胞内ROS水平升高.结果表明,PCB77和Cd^(2+)的共同暴露可引发联合肝细胞毒性,其毒性机理是线粒体膜电位下降和膜通透性增加,进而引发细胞凋亡.

Extensive research indicates that both polychlorinated biphenyls（ PCBs） and heavy metal cadmium（ Cd） could induce multiple toxicities including hepatotoxicity. However,the joint toxic effects and mechanisms caused by the combined exposure of PCBs and Cd have been rarely investigated. We here addressed their separate and joint toxicity with assessments in vitro in a representative human hepatic cell line SMMC-7721. Joint toxicity of these two chemicals was observed through cell viability assay after 48 h combined exposure with 25 μmol·L^（-1）PCB77 and20 μmol·L^（-1）Cd~（2＋（. Without impact on the integrity of cell membrane, combined exposure significantly decreased mitochondrial transmembrane potential and increased mitochondrial membrane permeability followed by induced cell apoptosis. Our results also showed the increased cellular ROS level upon combined exposure. In short,we demonstrated that the combined exposure of PCB77 and Cd incured joint toxicity,and the mechanism is that the change of the mitochondrial transmembrane potential induces cell apoptosis.