2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity.
In this review, we have examined the biochemical and toxic responses produced by halogenated aromatic hydrocarbons and have tried to develop a model for their mechanism of action. These compounds bind to a cellular receptor and evoke a sustained pleiotropic response. In many tissues this response consists of the expression of a battery of enzymes which are, for the most part, involved in drug metabolism, but in other tissues, those which develop toxicity, an additional set of genes is expressed which effects cellular involution, division, and/or differentiation. The toxicity of these compounds appears to be due to the sustained expression of a normal cellular regulatory system, of which we were previously unaware. In future investigations it is hoped that we will learn the nature and physiologic role of this regulatory system. Only then can we hope to understand the mechanism of toxicity of these compounds.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics; D002273:Carcinogens; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008297:Male; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000139:chemically induced; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000187:drug effects
D002273:Carcinogens; D004147:Dioxins; D006846:Hydrocarbons, Halogenated; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D001189:Aryl Hydrocarbon Hydroxylases