Microsomal Biphenyl Hydroxylation: the Formation of 3-Hydroxybiphenyl and Biphenyl Catechol

Abstract

3-Hydroxybiphenyl has been identified as a metabolite of biphenyl incubated with liver microsomes. Liver microsomes from hamster, mouse, and rabbit form 3-hydroxybiphenyl as well as 2-hydroxybiphenyl and 4-hydroxybiphenyl. The ratio of 2-hydroxybiphenyl to 3-hydroxybiphenyl is about 2:l with hamster and rabbit microsomes and 1:l with mouse microsomes. The major metabolite in all three species is 4-hydroxybiphenyl, but its relative amount also depends upon the species. Control rat liver microsomal hydroxylation of biphenyl yields 4-hydroxybiphenyl almost exclusively. 3-Methylcholanthrene or β-napthoflavone treatment of rats preferentially induces 2-hydroxybiphenyl formation, whereas increased amounts of 3- and 4-hydroxybiphenyl are formed after administration of phenobarbital. These results indicate that 3-hydroxybiphenyl is formed by a pathway different from that of either 2- or 4-hydroxybiphenyl. The existence of isotope effects for 3-hydroxybiphenyl formation but not for 2- or 4-hydroxybiphenyl formation from perdeuterobiphenyl suggests that this hydroxylation occurs at least partially via a direct hydroxylation pathway. In addition to the monohydroxylated products of biphenyl, the microsomal oxidation of biphenyl yields the catechol, 3,4-dihydroxybiphenyl. This same catechol is produced by the hydroxylation of either 3- or 4-hydroxybiphenyl. Studies with ¹⁸O suggest that 3,4-dihydroxybiphenyl is formed from biphenyl via two consecutive hydroxylations.