6-OHBDE-47 induces transcriptomic alterations of CYP1A1, XRCC2, HSPA1A, EGR1 genes and trigger apoptosis in HepG2 cells. (1st May 2018)

• Record Type: Journal Article
• Authors: Saquib, Quaiser; Siddiqui, Maqsood A.; Ahmad, Javed; Ansari, Sabiha M.; Al-Wathnani, Hend A.; Rensing, Christopher
• Is Part Of: Toxicology. Volume 400/401(2018)
• Page Start: 40
• Page End: 47
• Publication Date: 2018-05-01
• Subjects: 6-OHBDE-47 -- Toxicogenomics -- DNA damage -- Apoptosis -- Transcriptome -- ROS; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2018.03.007
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: 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.