Distribution and effects on cytochrome P450 system of two hexachlorobiphenyl isomers in the rat.
Tissue distribution and effects induced by 2,2',4,4',5,5'-hexachlorobiphenyl (245-HCB) on cytocrome P450 isozymes were compared with those of 2,2',3,3',6,6'-hexacholorobiphenyl (236-HCB). Male Wistar rats were given a single intragastric dose (23 mg/kg body wt) of either isomer, and killed after 72 h. At termination the tissue concentrations of 245-HCB were considerably higher than those of 236-HCB, suggesting a more effective metabolism of the latter. The binding affinity of 236-HCB to cytochrome P450 was higher and the magnitude of binding greater than of 245-HCB. 245-HCB-treatment elevated the hepatic concentration of cytochrome P450 and also the activities of 7-pentoxyresorufin O-depentylase (50-fold), aniline p-hydroxylase (2-fold) and 7-ethoxycoumarin O-deethylase (2-fold), a response typical of phenobarbital-type inducers. In the Western immunoblot of liver microsomes from 245-HCB treated rats, an increased amount of P450IIB 1/2 was detected by a monoclonal antibody 2-66-3, which specifically detects phenobarbital inducible isoenzymes. The minimum molecular mass of the P450 isozyme induced was 52 kDa. After 236-HCB administration, a weak inducing effect was observed.
Luotamo
M
M
Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki, Finland.
Elovaara
E
E
Raunio
H
H
Pelkonen
O
O
Riihimäki
V
V
Vainio
H
H
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C010498:2,3,6,2',3',6'-hexachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl