title: The cytological effects of HBCDs on human hepatocyte L02 and the potential molecular mechanism.
abstract: The concentration of hexabromocyclododecanes (HBCDs) in the environment media and organism samples are gradually rising with the increase of HBCDs usage. This study is designed to investigate the cytological effects of HBCDs on human hepatocyte L02 and explore the potential molecular mechanism. The results of CCK-8 assay showed that high concentration of HBCDs (>20 μM) significantly suppressed cell survival, while comparatively lower dose of HBCDs (10(-13)-10(-7)M) slightly stimulated cell proliferation (P < 0.05). In the mean time, high concentration HBCDs markedly induced cell apoptosis and DNA damage, accompanying with increase of intracellular Ca(2+)level and decrease of mitochondrial membrane potential (P < 0.05). ROS level induced by low concentration of HBCDs was comparatively lower than that by high concentration of HBCDs. In addition, low concentration HBCDs exposure (10(-13)-10(-7)M) resulted in up-regulation of PCNA protein expression level in a time-dependent manner. However, high concentration HBCDs exposure led to increase of Apaf-1 expression level. In conclusion, loss of mitochondrial membrane potential and activation of Apaf-1 mediated pathway involve the L02 cell apoptosis induced by high concentration HBCDs exposure. However, low concentration HBCDs exposure could stimulate cell proliferation of L02 cells, which might be associated with enhancement of PCNA expression.
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, PR China. peace74839@shu.edu.cn
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.forename: Wen
authors.initials: W
authors.lastname: Zou
authors.forename: Cen
authors.initials: C
authors.lastname: Chen
authors.forename: Fang Y
authors.initials: FY
authors.lastname: Zhong
authors.forename: Qiang Z
authors.initials: QZ
authors.lastname: Yu
authors.forename: Qi J
authors.initials: QJ
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D006842:Hydrocarbons, Brominated; D018809:Proliferating Cell Nuclear Antigen; C089796:hexabromocyclododecane