The effect of 3-methylcholanthrene, Aroclor 1254, and phenobarbital induction on the metabolism of biphenyl by rat and mouse 9000g supernatant liver fractions.
The metabolism of biphenyl in vitro in 9000 g supernatant fractions from livers of noninduced rats and mice was compared with the metabolism in similar liver fractions of rats and mice induced with 3-methylcholanthrene (3-MC), Aroclor 1254 and phenobarbital (PB). Analyses were carried out by open-tubular capillary gas chromatography and by gas chromatography/mass spectrometry. The major metabolite of biphenyl in all instances was 4-hydroxybiphenyl, and only very small amounts of diols were observed before induction. After induction by 3-MC, an increase was observed in all monohydroxybiphenyls for rat liver 9000 g supernatant fractions, and the 2,5- and 3,4-diols were present in greater amount. The effect of Aroclor 1254 induction resembled that observed for 3 MC induction. Induction of PB showed very little effect. For the mouse, induction with 3-MC resulted in an increase in all monohydroxybiphenyls and an increase in 2,5- and 3,4-diols. Induction with Aroclor 1254 resulted in an increase in 2-hydroxybiphenyl formation, but not in 4-hydroxylation. Thus the effects of 3-MC and Aroclor 1254 induction on biphenyl metabolism are similar in the rat but not in the mouse. Very little change was observed after PB induction. The effect of 3-MC induction (rat and mouse) on hydroxylation of monohydroxybiphenyls was to increase ortho- and para-hydroxylation in the hydroxy-substituted ring. Single-stage oxidations can be studied in vitro, but in vivo experiments are more informative when two or more stages of oxidation are involved. Although 2-hydroxylation of biphenyl is not a specific effect of cytochrome P1-r50 induction, biphenyl can be used as a test substance in animals to recognize this type of induction.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism*; D020111:Chlorodiphenyl (54% Chlorine); D004790:Enzyme Induction / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism*
D001140:Aroclors; D001713:Biphenyl Compounds; D020111:Chlorodiphenyl (54% Chlorine); D008748:Methylcholanthrene; D011078:Polychlorinated Biphenyls; D010634:Phenobarbital