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2,3,7,8-Tetrachlorodibenzo-p-dioxin Kills Immature Thymocytes By Ca2+-mediated Endonuclease Activation.
D. McConkey, P. Hartzell, S. K. Duddy, H. Håkansson, S. Orrenius
Published 1988 · Chemistry, Medicine
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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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