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Science 14 October 1988:
Vol. 242. no. 4876, pp. 256 - 259
DOI: 10.1126/science.3262923
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Articles

Science, Vol 242, Issue 4876, 256-259
Copyright © 1988 by American Association for the Advancement of Science

articles

2,3,7,8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation

DJ McConkey, P Hartzell, SK Duddy, H Hakansson, and S Orrenius

Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.

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.


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