Polychlorinated terphenyls: alterations in liver morphology and induction of cytochrome P-450.
Exposure of male rats to the polychlorinated terphenyl (PCT) mixtures Aroclor 5460 and Aroclor 5432 containing 60% and 32% (w/w) of chlorine, respectively, showed that the PCT mixture with a low degree of chlorination, Aroclor 5432, was a potent inducer of liver microsomal cytochrome P-450, aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase whereas Aroclor 5460 and the unchlorinated isomers o-, m- and p-terphenyl were weak inducers. Ultrastructurally, proliferation of SER but not RER, frequent occurrence of lysosomes containing partially degraded lipid material as well as an increased number and size of cytoplasmic lipid droplets were observed. These changes were most pronounced in Aroclor 5432 treated rats. Competition experiments with [3H]2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) for binding to the cytosolic receptor protein indicated the presence in Aroclor 5432, but not in Aroclor 5460, of components with receptor affinity. These components represent only a minor fraction of the mixture as judged by the 1900-fold excess necessary to displace 50% of the specific [3H]TCDD binding. Based on the biochemical results and the ultrastructural findings it is concluded that the PCT mixture Aroclor 5432 is a mixed type inducer of hepatic cytochrome P-450 in the rat. The presence in Aroclor 5432 of compounds capable of inducing AHH in vivo and of binding to the TCDD-receptor might be highly relevant with regard to the potential toxicity in view of the apparent correlation between affinity for the TCDD-receptor, induction of AHH activity and toxic properties for chlorinated aromatic hydrocarbons.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001667:Binding, Competitive; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D011080:Polychloroterphenyl Compounds / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism; D013730:Terphenyl Compounds / Q000633:toxicity*
D011080:Polychloroterphenyl Compounds; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D013730:Terphenyl Compounds; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases