Record Display for the EPA National Library Catalog


OLS Field Name OLS Field Data
Main Title Tributyltin and Dexamethasone Induce Apoptosis in Rat Thymocytes by Mutually Antagonistic Mechanisms.
Author Zucker, R. M. ; Elstein, K. H. ; Thomas, D. J. ; Rogers, J. M. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. ;ManTech Environmental Technology, Inc., Research Triangle Park, NC.
Publisher cJul 94
Year Published 1994
Report Number EPA/600/J-94/526;
Stock Number PB95-148888
Additional Subjects Dexamethasone ; Apoptosis ; Thymus gland ; Toxicology ; Rats ; Cultured cells ; Dose-response relationships ; Cell survival ; Cycloheximide ; Protein kinase C ; Deoxyribonucleic acids ; Reprints ; Tri-n-butyltin methoxide ; H 7
Library Call Number Additional Info Location Last
NTIS  PB95-148888 Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy. 03/06/1995
Collation 10p
We observed that rat thymocyte cultures exposed to 1.0 - 2.5 microM tri-n-butyltin methoxide (TBT) exhibited a rapid time- and concentration-dependent induction of apoptosis, with > 85% of cells exhibiting reduced DNA content within 1 hr after exposure to 2.0 - 2.5 microM TBT. Moreover, with continuous exposure to TBT, the DNA content of apoptotic nuclei increased with time, suggesting a reduced ability of DNA fragments to leave the nucleus of TBT-exposed cells following detergent-mediated cytolysis, possibly as a consequence of membrane/cytoplasm fixation. In contrast, exposure to 1.0 microM dexamethasone phosphate (DEX) resulted in a gradual time-dependent increase to approximately 45% induction of apoptosis by 6 hr (versus approximately 15% spontaneous induction in controls). However, simultaneous exposure to TBT and DEX resulted in a decreased response: TBT concentrations between 0.1 and 0.5 microM (which alone did not induce apoptosis) reduced the ability of DEX to induce apoptosis; at TBT concentrations greater than or equal to 1.0 microM, simultaneous exposure to DEX substantially decreased the extent of both TBT-induced cytotoxicity and apoptosis. Furthermore, while treatment with cycloheximide (CHX), a protein synthesis inhibitor, or H-7, a protein kinase C (PKC) inhibitor, completely blocked DEX-induced apoptosis, neither significantly reduced induction of apoptosis by TBT.