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RECORD NUMBER: 466 OF 502

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
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NTIS  PB95-148888 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 10p
Abstract 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.
Supplementary Notes Pub. in Toxicology and Applied Pharmacology, v127 n1 p163-170 Jul 94. See also PB92-164854. Prepared in cooperation with ManTech Environmental Technology, Inc., Research Triangle Park, NC.
NTIS Title Notes Journal article.
Title Annotations Reprint: Tributyltin and Dexamethasone Induce Apoptosis in Rat Thymocytes by Mutually Antagonistic Mechanisms.
Category Codes 57Y; 57F
NTIS Prices PC A02/MF A01
Primary Description 600/10
Document Type NT
Cataloging Source NTIS/MT
Control Number 503415379
Origin NTIS
Type CAT