Polybrominated　diphenyl　ethers　(PBDE)　have　been　widely　applied　as　flame　retardants　in　plastics,　polyurethane　foam,　paints,　and　synthetic　fabrics.　The　rising　PBDE　level　in　human　tissues　and　environment　has　led　to　concern　about　the　health　impact　of　exposure　to　PBDE.　The　2,2＇,4,4＇-tetrabromodiphenyl　ether　(BDE47),　the　dominant　PBDE　congener　found　in　the　environment　and　human　tissues,　has　been　shown　to　be　an　endocrine　disruptor.　It　has　also　been　reported　to　cause　liver　and　neurodevelopmental　toxicity.　BDE47　can　be　metabolized　to　6-OH-BDE47　and　6-MeO-BDE47.　So　far　little　has　been　reported　on　the　cytotoxicity　of　the　metabolites.　In　the　present　study,　the　cytotoxicity　of　the　two　metabolites　was　investigated　by　exposing　human　hepatoma　cell　line　HepG2　to　different　doses　of　6-OH-BDE47　and　6-MeO-BDE47.　The　cell　viability,　cell　cycle,　apoptosis,　DNA　damage,　micronucleus　levels,　and　oxidative　stress　response　were　studied.　The　results　indicated　that　both　metabolites　could　markedly　inhibit　the　proliferation　of　HepG2　cells　with　6-OH-BDE47　showing　a　stronger　effect,　and　significantly　increase　the　micronucleus　level　and　apoptosis　rate　in　a　dose-dependant　manner.　Moreover,　treatment　with　6-OH-BDE47　(＞=　0.5　mu　M)　resulted　in　a　marked　cell　cycle　block.　The　SCGE　experiments　revealed　that　both　metabolites　could　cause　DNA　damage　in　a　dose-dependant　manner.　Analysis　of　the　oxidative　stress　response　showed　that　6-OH-BDE47　treatment　(＞=　2.0　mu　M)　significantly　increased　intracellular　ROS　levels　as　indicated　by　GSH　depletion　and　elevation　of　SOD　level,　whereas　6-MeO-BDE47　showed　a　weaker　effect,　suggesting　that　oxidative　stress　might　play　a　role　in　the　cytotoxic　effects.　We　concluded　that　6-OH-BDE47　or　6-MeO-BDE47　exposure　was　able　to　induce　inhibition　of　cell　viability,　increase　of　apoptosis　rate,　cell　cycle　block,　and　DNA　damages,　which　might　involve　the　alterated　oxidative　stress　response　due　to　the　elevated　free　radicals　and　impaired　antioxidative　system.　(C)　2010　Wiley　Periodicals,　Inc.　Environ　Toxicol　26:　591-599,　2011.