title: Fluoride-induced genotoxicity in mouse bone marrow cells: effect of buthionine sulfoximine and N-acetyl-L-cysteine.
abstract: A significant level of reactive oxygen species generation was observed in sodium fluoride (NaF) treated mouse bone marrow cells (BMCs). Reduced glutathione (GSH) as a free radical scavenger could be an important determining factor in F-induced genotoxicity. We therefore attempted to monitor GSH to understand the mechanism of NaF-induced genotoxicity. NaF was injected intra-peritoneally in normal, buthionine sulfoximine (BSO) or N-acetyl-L-cysteine (NAC) treated mice (n = 5). After 13 h of NaF-treatment BMCs were collected to harvest them at the same divisional cycle and processed for analysis of cell cycle, induction of apoptosis and chromosomal aberrations (CAs). Level of GSH was also measured concomitantly. NaF induced significant CAs in all treatment groups except at 2.5 mg NaF kg(-1) body weight. BSO-treatment alone induced significantly high frequency of CAs. BSO treatment prior to injection of 2.5-7.5 mg NaF kg(-1) b.w. was found to increase the frequency of CAs, significantly when compared with the positive control group, but the level was not significant in case of higher doses of NaF treatment (15 and 30 mg kg(-1) b.w.). NaF-treated cells also showed a higher population of Annexin-V positive cells. NAC pre-treatment significantly reduced the extent of NaF-induced CAs, which clearly indicates the involvement of GSH in the NaF response. However, further study is warranted to evaluate the low synergistic effect of BSO on higher doses of NaF-induced CAs.
authors.affiliation: Radiation Genetics and Chemical Mutagenesis Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan-731235, West Bengal, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Podder
authors.forename: Ansuman
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Shelley
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Manas Ranjan
authors.initials: MR
authors.lastname: Ray
authors.forename: Anindita
authors.initials: A
authors.lastname: Chakraborty
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000737:chemistry / Q000187:drug effects*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000032:analysis; D008297:Male; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D012969:Sodium Fluoride / Q000633:toxicity*
chemical_list: D017304:Annexin A5; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D012969:Sodium Fluoride; D005978:Glutathione; D000111:Acetylcysteine