Study On Toxic Effect And Molecular Mechanism Of Dechlorane 603

Dechlorane 603(Dec603)is a chlorinated flame retardant that has been detected in various environmental and biotic matrices.As an analogue of Dechlorane plus(DP)and Dechlorane 602(Dec602),Dec603 can be persistent in the environment,bio-accumulated and biomagnified in biota.Moreover,Dec603 is more bio-accumulative than DP,posing a potential threat to human health and ecological environment.In this study,both estrogen receptor(ER)-negative human breast cancer cell(MDA-MB-231)and ER-positive human breast cancer cell(MCF-7)were used for in vitro Dec603 exposure.Based on the effects of Dec603 on cell viability,toxic mechanism was further verified by quantitative analysis of biomarkers in ER-mediated genomic and non-genomic pathways.The results in vitro demonstrated the estrogenic effect of Dec603.Dec603 can significantly increase MCF-7 cell proliferation at the concentration of 10-6M,in a dose-and time-dependent manner.Interestingly,Dec603 cannot promote MDA-MB-231 cell proliferation at the concentration of 10-10M?10-6M,suggesting the estrogenic effect of Dec603 is primarily mediated by ER.Further study on mechanism showed that Dec603 can significantly up-regulate mRNA and protein levels of ERa,as well as mRNA levels of some ER-targeted genes(c-myc,c-fos and cyclinDl)in MCF-7 cell,suggesting the estrogenic effect of Dec603 is by classic ERa-mediated genomic pathway.In addition,Dec603 exposure could increase the phosphorylative activation of ERK 1/2 and MEK,indicating ER-mediated non-genomic pathway(MAPK/ERK)may play a role in the estrogenic effects of Dec603.We demonstrated environmental related concentration of Dec603(10-6M)might have estrogenic effect,and the underlying mechanism is via up-regulating ER and ER-mediated genomic and non-genomic pathways.Our results undoubtedly provide theoretical basis for toxicological and biological risk assessment of Dec603.