title: Differential in vivo genotoxicity of arsenic trioxide in glutathione depleted mouse bone marrow cells: expressions of Nrf2/Keap1/P62.
abstract: Generation of reactive oxygen species is one of the major contributors in arsenic-induced genotoxicity where reduced glutathione (GSH) could be an important determining factor. To understand the role of endogenous GSH, arsenic trioxide (As2O3) was administered in buthionine sulfoximine (BSO)- and N-acetyl-L-cysteine (NAC)-treated mice. As2O3-induced significant chromosome aberrations (CAs) in all treatment groups compared with the control. BSO-treated mouse bone marrow cells showed significant CAs at a dose of 2 mg As2O3 kg(-1) b.w. Similar induction was not evident at 4 mg As2O3 kg(-1) b.w. and exhibited antagonistic effect at 8 mg As2O3 kg(-1) b.w. To understand this differential effect, expression pattern of Nrf2 was observed. Nrf2 expression increased following As2O3 treatment in a dose-dependent manner up to 4 mg As2O3 kg(-1) b.w after which no further increase was noticed. NAC pre-treatment significantly reduced the extent of As2O3-induced CAs suggesting the protective role of endogenous GSH against arsenic-induced genotoxicity.
authors.affiliation: Department of Zoology, Centre for Advanced Studies, Visva-Bharati University , Santiniketan, West Bengal , India and.
authors.forename: Ritu
authors.initials: R
authors.lastname: Srivastava
authors.forename: Shelley
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Anindita
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Ansuman
authors.initials: A
authors.lastname: Chattopadhyay
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002842:Chromatids / Q000187:drug effects / Q000473:pathology; D002869:Chromosome Aberrations / Q000139:chemically induced; D003598:Cytoskeletal Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005978:Glutathione / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010087:Oxides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001152:Arsenicals; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D008562:Membrane Glycoproteins; D009153:Mutagens; D051267:NF-E2-Related Factor 2; D009363:Neoplasm Proteins; C495636:Nfe2l2 protein, mouse; D028861:Nuclear Pore Complex Proteins; D010087:Oxides; C049312:nuclear pore protein p62; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D000077237:Arsenic Trioxide; D000111:Acetylcysteine
keywords: Arsenic trioxide; N-acetyl-l-cysteine; buthionine sulfoximine; genotoxicity; glutathione; mouse bone marrow cells