title: Tri-n-butyltin increases intracellular Zn(2+) concentration by decreasing cellular thiol content in rat thymocytes.
abstract: Effect of tri-n-butyltin (TBT), an environmental pollutant, on intracellular Zn(2+) concentration was tested in rat thymocytes to reveal one of cytotoxic profiles of TBT at nanomolar concentrations using a flow cytometer and appropriate fluorescent probes. TBT at concentrations of 30 nM or more (up to 300 nM) significantly increased the intensity of FluoZin-3 fluorescence, an indicator for intracellular Zn(2+) concentration, under external Ca(2+)- and Zn(2+)-free condition. Chelating intracellular Zn(2+) completely attenuated the TBT-induced augmentation of FluoZin-3 fluorescence. Result suggests that nanomolar TBT releases Zn(2+) from intracellular store site. Oxidative stress induced by hydrogen peroxide also increased the FluoZin-3 fluorescence intensity. The effects of TBT and hydrogen peroxide on the fluorescence were additive. TBT-induced changes in the fluorescence of FluoZin-3 and 5-chloromethylfluorescein, an indicator for cellular thiol content, were correlated with a coefficient of -0.962. Result suggests that the intracellular Zn(2+) release by TBT is associated with TBT-induced reduction of cellular thiol content. However, chelating intracellular Zn(2+) potentiated the cytotoxicity of TBT. Therefore, the TBT-induced increase in intracellular Zn(2+) concentration may be a type of stress responses to protect the cells.
authors: Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan.
authors: Toshihisa B
authors: TB
authors: Oyama
authors: Keisuke
authors: K
authors: Oyama
authors: Takuya
authors: T
authors: Kawanai
authors: Tomohiro M
authors: TM
authors: Oyama
authors: Erika
authors: E
authors: Hashimoto
authors: Masaya
authors: M
authors: Satoh
authors: Yasuo
authors: Y
authors: Oyama
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects; D011083:Polycyclic Compounds / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D015032:Zinc / Q000378:metabolism*
chemical_list: D004785:Environmental Pollutants; C451182:FluoZin-3; D005456:Fluorescent Dyes; D011083:Polycyclic Compounds; D013438:Sulfhydryl Compounds; D014220:Trialkyltin Compounds; C011559:tributyltin; D006861:Hydrogen Peroxide; D015032:Zinc