PMID- 21154881 OWN - NLM STAT- MEDLINE DCOM- 20120222 LR - 20131121 IS - 1099-1263 (Electronic) IS - 0260-437X (Linking) VI - 31 IP - 7 DP - 2011 Oct TI - Fluoride-induced genotoxicity in mouse bone marrow cells: effect of buthionine sulfoximine and N-acetyl-L-cysteine. PG - 618-25 LID - 10.1002/jat.1605 [doi] AB - 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. CI - Copyright (c) 2010 John Wiley & Sons, Ltd. FAU - Podder, Santosh AU - Podder S AD - Radiation Genetics and Chemical Mutagenesis Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan-731235, West Bengal, India. FAU - Chattopadhyay, Ansuman AU - Chattopadhyay A FAU - Bhattacharya, Shelley AU - Bhattacharya S FAU - Ray, Manas Ranjan AU - Ray MR FAU - Chakraborty, Anindita AU - Chakraborty A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101210 PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (Annexin A5) RN - 0 (Reactive Oxygen Species) RN - 5072-26-4 (Buthionine Sulfoximine) RN - 8ZYQ1474W7 (Sodium Fluoride) RN - GAN16C9B8O (Glutathione) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*pharmacology MH - Animals MH - Annexin A5/metabolism MH - Apoptosis/drug effects MH - Bone Marrow Cells/chemistry/*drug effects MH - Buthionine Sulfoximine/*pharmacology MH - Cell Cycle/drug effects MH - Chromosome Aberrations/drug effects MH - DNA Damage/*drug effects MH - Dose-Response Relationship, Drug MH - Glutathione/analysis MH - Male MH - Mice MH - Reactive Oxygen Species/metabolism MH - Sodium Fluoride/*toxicity EDAT- 2010/12/15 06:00 MHDA- 2012/02/23 06:00 CRDT- 2010/12/15 06:00 PHST- 2010/07/01 00:00 [received] PHST- 2010/08/02 00:00 [revised] PHST- 2010/09/01 00:00 [accepted] PHST- 2010/12/15 06:00 [entrez] PHST- 2010/12/15 06:00 [pubmed] PHST- 2012/02/23 06:00 [medline] AID - 10.1002/jat.1605 [doi] PST - ppublish SO - J Appl Toxicol. 2011 Oct;31(7):618-25. doi: 10.1002/jat.1605. Epub 2010 Dec 10.