Cytotoxic Effects Of Cd And PCB77 Complex Erythroid Precursor

Heavy metal cadmium?Cd?and polychlorinated biphenyls?PCBs?are two types of pollutants that are present in the environment simultaneously,posing a threat to human health.In this paper,the human erythroleukemia cell line HEL and the hepatoma cell line SMMC-7721 were used as cell exposure models.Single or complex erythroid precursors toxic effects of Cd and 3,3',4,4'-tetrachlorobiphenyl?PCB77?was evaluated by using cell biology and molecular biology method,and to verify them in hepatic cell lines,and then explore the complex toxicity mechanism triggered by Cd and PCB77.The exposure concentrations of Cd and PCB77 were 1?mol·L^-1,15?mol·L^-1,and40?mol·L^-1,respectively,and the common exposure concentrations were their mixtures.Cell and sub-cytotoxic effects were explored by AB method,MTT method,LDH method and JC-1 method.The results showed that exposures could decrease mitochondrial succinate dehydrogenase activity and mitochondrial membrane potential in both HEL and SMMC-7721 cells,resulting in atrophy of cell morphology.Multi-factor linear regression model analysis showed that the combined effects of Cd and PCB77 on the two cell lines were additive.The real-time quantitative polymerase chain reaction?qRT-PCR?and Western blotting methods were used to explore the mechanism of toxicity.The results showed that the combined exposure of Cd and PCB77 can stimulate the expression of related antioxidant genes at the mRNA level by activating the elF2?-Atf4 signaling pathway.The expression of GSTP1 at high concentration?40?M?was increased by 10-fold,17-fold and230-fold compared with the blank control group,Cd and PCB77 alone.but promoted the increase of ROS level in HEL cells.After 48h treatment with Cd and PCB77,the cells showed obvious apoptosis.Cd and PCB77 also interfere with iron metabolism in HEL cells.Separate exposure promotes intracellular free iron LIP levels,while LIP levels in the co-exposed group show a decreasing trend.Cd exposure caused a decrease in the expression of ferritin in HEL cells,while exposure to PCB77 increased the expression of ferritin in HEL cells.Exposure of Cd and PCB77 interferes with energy metabolism in SMMC-7721 cells,which is characterized by decreased intracellular ATPase activity and mitochondrial membrane potential,resulting in changes in ATP content;enhanced fructose1,6-bisphosphatase?FBP?activity and promotion of gluconeogenesis.It was found that combined exposure of Cd and PCB77 affects the content of triglyceride?TG?and cholesterol,causing disorder of intracellular lipid metabolism.This study will provide a theoretical basis and methodological reference for the cytotoxic effects of persistent organic pollutants and heavy metal exposure.