Hazards of low dose flame-retardants (BDE-47 and BDE-32): Influence on transcriptome regulation and cell death in human liver cells

Quaiser Saquib; Maqsood A Siddiqui; Javed Ahmed; Abdullah Al-Salim; Sabiha M Ansari; Mohammad Faisal; Abdulaziz A Al-Khedhairy; Javed Musarrat; Hend A AlWathnani; Abdulrahman A Alatar; Saud A Al-Arifi

doi:10.1016/j.jhazmat.2016.01.025

Hazards of low dose flame-retardants (BDE-47 and BDE-32): Influence on transcriptome regulation and cell death in human liver cells

J Hazard Mater. 2016 May 5:308:37-49. doi: 10.1016/j.jhazmat.2016.01.025. Epub 2016 Jan 13.

Affiliations

¹ 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.
² 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.
³ Department of Botany & Microbiology, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁴ Zoology Department, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁵ 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.

PMID: 26808241
DOI: 10.1016/j.jhazmat.2016.01.025

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.

Keywords: BDE-32; BDE-47; Cell death; Flame-retardants; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Death / drug effects
Cell Survival / drug effects
Comet Assay
DNA Damage
Flame Retardants / toxicity*
Halogenated Diphenyl Ethers / toxicity*
Hep G2 Cells
Humans
Liver / cytology
Membrane Potential, Mitochondrial / drug effects
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism
Transcriptome / drug effects

Substances

Flame Retardants
Halogenated Diphenyl Ethers
RNA, Messenger
Reactive Oxygen Species
2,2',4,4'-tetrabromodiphenyl ether