Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta.
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), a widespread environmental contaminant, may elicit its effects by altering gene expression in susceptible cells. Five TCDD-responsive complementary DNA clones were isolated from a human keratinocyte cell line. One of these clones encodes plasminogen activator inhibitor-2, a factor that influences growth and differentiation by regulating proteolysis of the extracellular matrix. Another encodes the cytokine interleukin-1 beta. Thus, TCDD alters the expression of growth regulatory genes and has effects similar to those of other tumor-promoting agents that affect both inflammation and differentiation.
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
T R
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Sutter
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Guzman
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Dold
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Greenlee
D001483:Base Sequence; D001790:Blood Physiological Phenomena; D015152:Blotting, Northern; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015849:Plasminogen Inactivators; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D007375:Interleukin-1; D015849:Plasminogen Inactivators; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D003513:Cycloheximide; D002118:Calcium