2,3,7,8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation.
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.
McConkey
D J
DJ
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Hartzell
P
P
Duddy
S K
SK
Håkansson
H
H
Orrenius
S
S
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
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