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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Atrophy
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Body Weight / drug effects
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Calcimycin / pharmacology
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Calcium / metabolism
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Cell Survival / drug effects
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DNA / drug effects
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DNA / metabolism*
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Dioxins / toxicity*
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Dose-Response Relationship, Drug
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Drug Synergism
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Endonucleases / metabolism
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Glucocorticoids / pharmacology*
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Kinetics
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Male
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Methylprednisolone / pharmacology
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Organ Size / drug effects
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Polychlorinated Dibenzodioxins / administration & dosage
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Polychlorinated Dibenzodioxins / pharmacology
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Polychlorinated Dibenzodioxins / toxicity*
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Rats
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Rats, Inbred Strains
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Thymus Gland / drug effects
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Thymus Gland / metabolism
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Thymus Gland / pathology*
Substances
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Dioxins
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Glucocorticoids
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Polychlorinated Dibenzodioxins
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Calcimycin
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DNA
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Endonucleases
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Calcium
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Methylprednisolone