2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) kills glucocorticoid-sensitive thymocytes in vivo.
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.
McConkey
D J
DJ
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Orrenius
S
S
D000818:Animals; D001284:Atrophy; D001835:Body Weight / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004720:Endonucleases / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D004147:Dioxins; D005938:Glucocorticoids; D000072317:Polychlorinated Dibenzodioxins; D000001:Calcimycin; D004247:DNA; D004720:Endonucleases; D002118:Calcium; D008775:Methylprednisolone