Rapid cytoskeleton modification in thymocytes induced by the immunotoxicant tributyltin.
Treatment of rat thymocytes with the immunotoxic environmental pollutant tributyltin (TBT) caused a rapid decrease in the F-actin content resulting in the depolymerization of 80% of the total thymocyte F-actin in 10 min. Removal of extracellular Ca2+ and pretreatment of the thymocytes with the intracellular Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N',N',N',N',-tetraacetic acid, abolished the TBT-induced increase in cytosolic free Ca2+ concentration but reduced the depolymerization of F-actin by only 25%. Thus, the data suggest that 75% of the decrease in F-actin content in the thymocytes was due to other effects of TBT. Pretreatment of rat thymocytes with the alkylating agent N-ethylmaleimide completely inhibited TBT-induced F-actin disruption, suggesting that thiol group modification is involved. The TBT-induced decrease in thymocyte F-actin was not specific for any particular subpopulation of thymocytes. Furthermore, triphenyltin and the metabolite of TBT, dibutyltin, were also found to induce depolymerization of thymocyte F-actin, whereas nonimmunotoxic organotin compounds like trimethyltin and triethyltin had no effect. In conclusion, TBT was found to induce rapid depolymerization of F-actin in thymocytes through both Ca(2+)-dependent and Ca(2+)-independent mechanisms, suggesting that the potent immunotoxic effect of TBT may involve cytoskeletal modifications in addition to the perturbation of thymocyte Ca2+ homeostasis reported previously.
Chow
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SC
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Orrenius
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D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009947:Organotin Compounds / Q000633:toxicity; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D014220:Trialkyltin Compounds / Q000633:toxicity*
D000199:Actins; D009947:Organotin Compounds; D011108:Polymers; D014220:Trialkyltin Compounds; C056189:di-n-butyltin; C011559:tributyltin; D004533:Egtazic Acid; C030665:triphenyltin; C020735:dibutyldichlorotin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D005033:Ethylmaleimide; D002118:Calcium