Possible correlation between induction modes of hepatic enzymes by PCBs and their toxicity in rats.
Acute toxicity of individual PCBs, which were categorized as either phenobarbital (PB)- or 3-methylcholanthrene (MC)-type inducers, was examined in young male Wistar rats, comparing their effects on growth rate, organ weight and liver lipid content, 5 days after a single i.p. injection. PB-type PCBs (2,4,3',4'- and 2,5,2'5'-tetrachlorobiphenyl), which slightly increased a content of cytochrome P450, did not show any significant toxicity at a dose of 100 mg/kg. On the contrary, MC-type PCBs (3,4,5,3',4'-pentachloro- and 3,4,5,3',4',5'-hexachlorobiphenyl), which markedly increased a content of cytochrome P448, strongly reduced growth rate and weights of thymus and spleen at a dose of 10 mg/kg. Liver enlargement accompanied by fatty liver was also observed only with MC-type PCBs. 3,4,3',4'-Tetrachlorobiphenyl was also toxic at a dose of 50 mg/kg, in keeping with its weak MC-type-inducing ability. Pretreatment with MC affected neither growth rate, spleen weight, nor liver lipid content. These results suggest that the toxic potency of PCBs is related to their MC-type inducing ability, but the toxic characteristics are different from those of MC itself.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002458:Cell Fractionation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010634:Phenobarbital; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D011808:Quinone Reductases / Q000378:metabolism; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D006899:Mixed Function Oxygenases; D010089:Oxidoreductases, N-Demethylating; D011808:Quinone Reductases; D010634:Phenobarbital