title: Hazards of low dose flame-retardants (BDE-47 and BDE-32): Influence on transcriptome regulation and cell death in human liver cells.
abstract: We have evaluated the in vitro low dose hepatotoxic effects of two flame-retardants (BDE-47 and BDE-32) in HepG2 cells. Both congeners declined the viability of cells in MTT and NRU cell viability assays. Higher level of intracellular reactive oxygen species (ROS) and dysfunction of mitochondrial membrane potential (ΔΨm) were observed in the treated cells. Comet assay data confirmed the DNA damaging potential of both congeners. BDE-47 exposure results in the appearance of subG1 apoptotic peak (30.1%) at 100 nM, while BDE-32 arrested the cells in G2/M phase. Among the set of 84 genes, BDE-47 induces downregulation of majority of mRNA transcripts, whilst BDE-32 showed differential expression of transcripts in HepG2. The ultrastructural analysis revealed mitochondrial swelling and degeneration of cristae in BDE-47 and BDE-32 treated cells. Overall our data demonstrated the hepatotoxic potential of both congeners via alteration of vital cellular pathways.
authors.affiliation: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; A.R. Al-Jeraisy Chair for DNA Research, Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: quaiser.saquib0@gmail.com.
authors.forename: Quaiser
authors.initials: Q
authors.lastname: Saquib
authors.affiliation: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; A.R. Al-Jeraisy Chair for DNA Research, Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Maqsood A
authors.initials: MA
authors.lastname: Siddiqui
authors.affiliation: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; A.R. Al-Jeraisy Chair for DNA Research, Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Javed
authors.initials: J
authors.lastname: Ahmed
authors.affiliation: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia; A.R. Al-Jeraisy Chair for DNA Research, Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Salim
authors.affiliation: Department of Botany & Microbiology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Sabiha M
authors.initials: SM
authors.lastname: Ansari
authors.affiliation: Department of Botany & Microbiology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Faisal
authors.affiliation: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulaziz A
authors.initials: AA
authors.lastname: Al-Khedhairy
authors.affiliation: Department of Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh 202002, India; Baba Ghulam Shah Badshah University, Rajouri 185131, Jammu and Kashmir, India.
authors.forename: Javed
authors.initials: J
authors.lastname: Musarrat
authors.affiliation: Department of Botany & Microbiology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Hend A
authors.initials: HA
authors.lastname: AlWathnani
authors.affiliation: Department of Botany & Microbiology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulrahman A
authors.initials: AA
authors.lastname: Alatar
authors.affiliation: Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Saud A
authors.initials: SA
authors.lastname: Al-Arifi
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000166:cytology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C511295:2,2',4,4'-tetrabromodiphenyl ether
keywords: BDE-32; BDE-47; Cell death; Flame-retardants; Oxidative stress