Cytotoxicity evaluation of three pairs of hexabromocyclododecane (HBCD) enantiomers on Hep G2 cell.
Hexabromocyclododecanes (HBCDs) are additive brominated flame retardants mainly used in plastics and textiles. At the present time, these compounds are found in almost all environmental and human samples. In order to evaluate the environmental safety and health risk of HBCDs, the enantiomerically pure alpha-, beta-, and gamma-HBCD were prepared using high performance liquid chromatography (HPLC) on a PM-beta-CD column and the cytotoxicities of their enantiomers were evaluated in Hep G2 cells. Results from the 3-(4,5-dimethylthioazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), resazurin reduction and lactate dehydrogenase (LDH) release assays showed a good agreement that the order of cytotoxicity was gamma-HBCDbeta-HBCD>alpha-HBCD, and that significantly lower cell viability and higher LDH release were observed in all (+)-enantiomers ((+) alpha-, (+) beta- and (+) gamma-HBCD) than the corresponding (-)-forms ((-) alpha-, (-) beta- and (-) gamma-HBCD). Additionally, the formation of reactive oxygen species (ROS) induced by these HBCD enantiomers were detected. The positive correlation between the LDH release and ROS formation demonstrated that the toxic mechanism might be mediated by oxidative damage. These results suggest that environmental and human health risks of HBCDs must be evaluated at the level of individual enantiomers.
Zhang
Xiaoling
X
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, #7 Donghu South Road, Wuhan, China.
Yang
Fangxing
F
Xu
Chao
C
Liu
Weiping
W
Wen
Sheng
S
Xu
Ying
Y
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005411:Flame Retardants / Q000633:toxicity*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000737:chemistry / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism
D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D017382:Reactive Oxygen Species; C089796:hexabromocyclododecane; D007770:L-Lactate Dehydrogenase