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...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1988-10, Vol.242 (4876), p.256-259 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | MCCONKEY, D. J HARTZELL, P DUDDY, S. K HAKANSSON, H ORRENIUS, S |
| description | 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. |
| doi_str_mv | 10.1126/science.3262923 |
| format | Article |
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J ; HARTZELL, P ; DUDDY, S. K ; HAKANSSON, H ; ORRENIUS, S</creator><creatorcontrib>MCCONKEY, D. J ; HARTZELL, P ; DUDDY, S. K ; HAKANSSON, H ; ORRENIUS, S</creatorcontrib><description>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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.3262923</identifier><identifier>PMID: 3262923</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Aminoquinolines ; Animals ; Biochemistry ; Biological and medical sciences ; Calcium - metabolism ; Calcium - pharmacology ; Cell Survival - drug effects ; Cycloheximide - pharmacology ; Cytosol - metabolism ; Deoxyribonuclease I - metabolism ; Dioxins - pharmacology ; DNA - metabolism ; Enzyme Activation - drug effects ; Fluorescent Dyes ; Fundamental and applied biological sciences. 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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.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>3262923</pmid><doi>10.1126/science.3262923</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1988-10, Vol.242 (4876), p.256-259 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; American Association for the Advancement of Science |
| subjects | Aminoquinolines Animals Biochemistry Biological and medical sciences Calcium - metabolism Calcium - pharmacology Cell Survival - drug effects Cycloheximide - pharmacology Cytosol - metabolism Deoxyribonuclease I - metabolism Dioxins - pharmacology DNA - metabolism Enzyme Activation - drug effects Fluorescent Dyes Fundamental and applied biological sciences. Psychology Fundamental immunology Genetics Glucocorticoids - pharmacology Kinetics Polychlorinated Dibenzodioxins - pharmacology Rats T-Lymphocytes - drug effects Thymus Gland - drug effects Thymus Gland - metabolism |
| title | 2,3,7,8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation |
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