@article {Haugen212, author = {D A Haugen}, title = {Biphenyl metabolism by rat liver microsomes: regioselective effects of inducers, inhibitors, and solvents.}, volume = {9}, number = {3}, pages = {212--218}, year = {1981}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Examination of the regioselective metabolism of biphenyl was explored as a means of characterizing different forms of cytochrome P-450 in microsomal and purified mono-oxygenase systems. In the present study the effects of the inducers phenobarbital and 3-methylcholanthrene, the inhibitors 7,8-benzoflavone and 1-benzylimidazole, and the solvents methanol, acetone, and dimethyl sulfoxide on the 2-, 3-, and 4-hydroxylation of biphenyl and the O-deethylation of 7-ethoxycoumarin by rat liver microsomes were examined. Phenobarbital pretreatment primarily induced 2- and 3-hydroxylation, the latter most dramatically. 3-Methylcholanthrene pretreatment induced 2- and 3-hydroxylation to similar extents. The inhibitors and solvents had regioselective effects on biphenyl metabolism that were characteristic of the uninduced, phenobarbital-induced, and 3-methylcholanthrene-induced microsomes. The presence of multiple forms of cytochrome P-450 in uninduced microsomes is indicated by the regioselective effects of the solvents and the inhibitors. The 3-methylcholanthrene-dependent increases in 2- and 3-hydroxylation appear due to induction of a single form of cytochrome P-450, as indicated by similar dose-response relationships and similar changes in sensitivity to the inhibitors. The phenobarbital-dependent increases in 2- and 3-hydroxylation appear due to the induction of two forms of cytochrome P-450, as indicated by different changes in sensitivity to the effects of dimethyl sulfoxide and 7,8-benzoflavone. The results indicate that examination of the regioselectivity of biphenyl metabolism is a useful approach for characterizing microsomal mono-oxygenases, and they suggest that the approach may also be useful in the characterization of purified mono-oxygenase systems.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/9/3/212}, eprint = {https://dmd.aspetjournals.org/content/9/3/212.full.pdf}, journal = {Drug Metabolism and Disposition} }