2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) kills glucocorticoid-sensitive thymocytes in vivo

David J. McConkey; Sten Orrenius

doi:10.1016/S0006-291X(89)80101-9

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) kills glucocorticoid-sensitive thymocytes in vivo

David J. McConkey, Sten Orrenius

Urology

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

The effect of in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on glucocorticoid- and calcium ionophore-induced DNA fragmentation in rat thymocytes was investigated. TCDD dose-dependently abolished DNA fragmentation in response to both agents after 7 days of exposure. Analysis of the time dependence of the effect revealed that after 1 or 2 days TCDD potentiated DNA fragmentation in untreated and glucocorticoid-treated thymocyte suspensions relative to controls. The DNA fragmentation in untreated thymocyte suspensions from TCDD-treated rats was completely prevented by inhibitors that block glucocorticoid-induced thymocyte suicide. Our results suggest that TCDD-induced thymic atrophy is due to Ca²⁺-dependent endonuclease activation.

Original language	English (US)
Pages (from-to)	1003-1008
Number of pages	6
Journal	Biochemical and biophysical research communications
Volume	160
Issue number	3
DOIs	https://doi.org/10.1016/S0006-291X(89)80101-9
State	Published - May 15 1989

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/S0006-291X(89)80101-9

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title = "2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) kills glucocorticoid-sensitive thymocytes in vivo",

abstract = "The effect of in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on glucocorticoid- and calcium ionophore-induced DNA fragmentation in rat thymocytes was investigated. TCDD dose-dependently abolished DNA fragmentation in response to both agents after 7 days of exposure. Analysis of the time dependence of the effect revealed that after 1 or 2 days TCDD potentiated DNA fragmentation in untreated and glucocorticoid-treated thymocyte suspensions relative to controls. The DNA fragmentation in untreated thymocyte suspensions from TCDD-treated rats was completely prevented by inhibitors that block glucocorticoid-induced thymocyte suicide. Our results suggest that TCDD-induced thymic atrophy is due to Ca2+-dependent endonuclease activation.",

author = "McConkey, {David J.} and Sten Orrenius",

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T1 - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) kills glucocorticoid-sensitive thymocytes in vivo

AU - McConkey, David J.

AU - Orrenius, Sten

N1 - Funding Information: supported by grants from the Swedish Medical Research Council (Project No. 03X-

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N2 - The effect of in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on glucocorticoid- and calcium ionophore-induced DNA fragmentation in rat thymocytes was investigated. TCDD dose-dependently abolished DNA fragmentation in response to both agents after 7 days of exposure. Analysis of the time dependence of the effect revealed that after 1 or 2 days TCDD potentiated DNA fragmentation in untreated and glucocorticoid-treated thymocyte suspensions relative to controls. The DNA fragmentation in untreated thymocyte suspensions from TCDD-treated rats was completely prevented by inhibitors that block glucocorticoid-induced thymocyte suicide. Our results suggest that TCDD-induced thymic atrophy is due to Ca2+-dependent endonuclease activation.

AB - The effect of in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on glucocorticoid- and calcium ionophore-induced DNA fragmentation in rat thymocytes was investigated. TCDD dose-dependently abolished DNA fragmentation in response to both agents after 7 days of exposure. Analysis of the time dependence of the effect revealed that after 1 or 2 days TCDD potentiated DNA fragmentation in untreated and glucocorticoid-treated thymocyte suspensions relative to controls. The DNA fragmentation in untreated thymocyte suspensions from TCDD-treated rats was completely prevented by inhibitors that block glucocorticoid-induced thymocyte suicide. Our results suggest that TCDD-induced thymic atrophy is due to Ca2+-dependent endonuclease activation.

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) kills glucocorticoid-sensitive thymocytes in vivo

Abstract

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