title: Genotoxicity of several polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs, and their mechanisms of toxicity.
abstract: Polybrominated diphenyl ethers (PBDEs) have been extensively utilized as flame retardants, and recently there has been concern about potential adverse effects in humans and wildlife. Their hydroxylated analogs (OH-BDEs) have received increasing attention due to their potential for endocrine and neurological toxicities. However, the potentials and mechanisms of genotoxicity of these brominated compounds have scarcely been investigated. In the present study, genotoxicity of tetra-BDEs, penta BDE, octa-BDE, deca-BDE, and tetra-OH-BDEs were investigated by use of chicken DT40 cell lines including wild-type cells and a panel of mutant cell lines deficient in DNA repair pathways. Tetra-BDEs have greater genotoxic potential than do the other BDEs tested. OH-tetra-BDEs were more genotoxic than tetra-BDEs. DT40 cells, deficient in base excision repair (Polβ(-/-)) and translesion DNA synthesis (REV3(-/-)) pathways, were hypersensitive to the genotoxic effects of tetra-BDEs and OH-tetra-BDEs. The observation of chromosomal aberrations and gamma-H2AX assay confirmed that the studied brominated compounds caused double strand breaks. Pretreatment with N-acetyl-l-cysteine (NAC) significantly rescued the Polβ(-/-) and REV3(-/-) mutants, which is consistent with the hypothesis that PBDEs and OH-BDEs cause DNA damage mediated through reactive oxygen species (ROS). Some tetra-BDEs and OH-tetra-BDEs caused base damage through ROS leading to replication blockage and subsequent chromosomal breaks.
authors.affiliation: School of Public Health, Seoul National University, Seoul, 151-742, Korea.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Ji
authors.forename: Kyungho
authors.initials: K
authors.lastname: Choi
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Javed
authors.initials: J
authors.lastname: Musarrat
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006900:Hydroxylation; D009152:Mutagenicity Tests
chemical_list: D055768:Halogenated Diphenyl Ethers