RT Journal Article
SR Electronic
T1 The effect of 3-methylcholanthrene, Aroclor 1254, and phenobarbital induction on the metabolism of biphenyl by rat and mouse 9000g supernatant liver fractions.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 103
OP 107
VO 9
IS 2
A1 K Halpaap-Wood
A1 E C Horning
A1 M G Horning
YR 1981
UL http://dmd.aspetjournals.org/content/9/2/103.abstract
AB 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.