calcimycin and Atrophy

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.

Topics: Animals; Atrophy; Body Weight; Calcimycin; Calcium; Cell Survival; Dioxins; DNA; Dose-Response Relationship, Drug; Drug Synergism; Endonucleases; Glucocorticoids; Kinetics; Male; Methylprednisolone; Organ Size; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains; Thymus Gland