title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation.
abstract: Suspensions of thymocytes from young rats were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which resulted in a sustained increase in cytosolic free Ca2+ concentration followed by DNA fragmentation and loss of cell viability. Both the Ca2+ increase and DNA fragmentation were prevented in cells treated with the inhibitor of protein synthesis, cycloheximide, and DNA fragmentation and cell killing were not detected when cells were incubated in a "Ca2+-free" medium or pretreated with high concentrations of the calcium probe, quin-2 tetraacetoxymethyl ester. These results indicate that TCDD can kill immature thymocytes by initiating a suicide process similar to that previously described for glucocorticoid hormones.
authors.affiliation: Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: D J
authors.initials: DJ
authors.lastname: McConkey
authors.forename: P
authors.initials: P
authors.lastname: Hartzell
authors.forename: S K
authors.initials: SK
authors.lastname: Duddy
authors.forename: H
authors.initials: H
authors.lastname: Håkansson
authors.forename: S
authors.initials: S
authors.lastname: Orrenius
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004147:Dioxins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005456:Fluorescent Dyes; D005938:Glucocorticoids / Q000494:pharmacology; D007700:Kinetics; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D004147:Dioxins; D005456:Fluorescent Dyes; D005938:Glucocorticoids; D000072317:Polychlorinated Dibenzodioxins; C035738:Quin2-acetoxymethyl ester; D004247:DNA; D003513:Cycloheximide; D003850:Deoxyribonuclease I; D002118:Calcium