2,3,7,8-Tetrachlorodibenzo-p-dioxin Kills Immature Thymocytes by Ca$^{2+}$ -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 Ca$^{2+}$ concentration followed by DNA fragmentation and loss of cell viability. Both the Ca$^{2+}$ increase and DNA fragmentation were...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1988-10, Vol.242 (4876), p.256-259
Main Authors: McConkey, David J., Hartzell, Pia, Duddy, Steven K., Håkansson, Helen, Orrenius, Sten
Format: Article
Language:English
Subjects:
Apoptosis
B lymphocytes
Chromatin
DNA
DNA fragmentation
Epithelial cells
Glucocorticoids
T lymphocytes
Thymocytes
Viability
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Summary: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 Ca$^{2+}$ concentration followed by DNA fragmentation and loss of cell viability. Both the Ca$^{2+}$ 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 ``Ca$^{2+}$-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.
ISSN:0036-8075
1095-9203