Mechanisms of the biological effects of PCBs, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in experimental animals.
Polychlorinated biphenyls, certain polychlorinated dibenzo-p-dioxins and certain polychlorinated dibenzofurans cause a variety of biological effects in experimental animals. The mechanism of the induction of certain enzymes is perhaps best understood. That is, there is binding of certain chlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans to a receptor, translocation of the compound-receptor complex into the nucleus followed by an increased activity of a number of enzymes in the cell. Although the concentration of this receptor in various tissues of some mouse strains correlates well with the intensity of some of the biological effects observed in the mouse strains exposed to these compounds, this correlation apparently does not extend across various species. The current evidence suggests that the acute toxic effects of TCDD in various species is in some way associated with binding of TCDD to the receptor. However, biological effects of TCDD in addition to those resulting from binding to the receptor may be required to produce acute toxicity and, perhaps, other effects. The acute toxic effects of TCDD are probably caused by the parent compound rather than metabolites; however, this conclusion must be viewed as tentative. Also, it cannot be excluded at this time that biological effects other than acute toxicity may be caused by metabolites of TCDD. Finally, the acute toxic effects of TCDD appear not to be related, at least not directly, to the rate of metabolism of TCDD in experimental animals nor to the half-life of excretion.
Neal
R A
RA
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001572:Benzofurans / Q000633:toxicity*; D006224:Cricetinae; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D000882:Haplorhini; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases