6-OHBDE-47 induces transcriptomic alterations of CYP1A1, XRCC2, HSPA1A, EGR1 genes and trigger apoptosis in HepG2 cells

In this study, HepG2 cells were exposed to 6-hydroxy- 2,2′,4,4′-tetrabromodiphenyl ether (6-OH-BDE-47) for 3 and 6 days for monitoring cytotoxic effects and alterations in its transcriptomic profile. MTT assay showed that cells exposed to 6-OH-BDE-47 (50 nM) exhibited 48.5% and 53.7% decline in cell survival after 3 and 6 days. Neutral red uptake (NRU) assay also demonstrated 47.1% and 56% reduction in cell survival at 50 nM, indicating lysosomal toxicity. The flow cytometric data confirmed an increase in intracellular reactive oxygen species (ROS) and mitochondrial dysfunction (ΔΨm). In comet assay, HepG2 cells exposed to 6-OH-BDE-47 (50 nM) showed 7.6-fold greater DNA damage. Cell cycle data revealed G2/M arrest at 10 and 25 nM after 3 days of exposure, while 50 nM induced mild apoptotic effect. The intensity of apoptosis increased after 6 days of exposure with 21.5%, 47% and 99.1% of cells recorded in subG1 apoptotic phase vis-à- vis the control showed 14.5% background apoptotic cells. Transcriptome analysis of 6-OH-BDE-47 (25 nM, 3 days) treated cells revealed cross talk between vital pathways. Especially, the genes involved in oxidative or metabolic stress, heat shock, growth arrest and senescence were differentially up- and down regulated to orchestrate the cellular toxicity and triggering apoptosis in HepG2 cells.