Biphenyl hydroxylation and its induction differ between montane voles and Swiss Webster mice

Abstract

Hepatic microsomes from female montane voles, Microtus montanus, metabolized biphenyl to 4-hydroxybiphenyl (359 ng/mg microsomal protein/min), 3-hydroxybiphenyl (49 ng/mg/min), and 2-hydroxybiphenyl (29 ng/mg/min). Phenobarbital treatment of the voles (ip) induced in vitro biphenyl hydroxylations by about 324, 865, and 445% for 4-, 3- and 2-hydroxylation, respectively. Comparable studies were made of female, white Swiss Webster mice. The major microsomal metabolite was 4-hydroxybiphenyl (1010 ng/mg/min) but more 2-hydroxybiphenyl (118 ng/mg/min) was formed than 3-hydroxybiphenyl (92 ng/mg/min). Phenobarbital treatment of the mice barely changed biphenyl 2-hydroxylation (−1.3%) but did raise 3- and 4-hydroxylation (55 and 211%, respectively). Treatment of voles with 3-methylcholanthrene raised biphenyl 2-, 3-, and 4-hydroxylation by about 81, 50, and 47%, respectively, whereas in mice the increases were 176, 41, and 31%, respectively. β-Naphthoflavone treatment had similar effects. The vole liver microsomes were dependent upon NADPH for biphenyl hydroxylation. The carbon monoxide difference spectra of reduced cytochrome in the microsomes show a peak at 450.4 nm. This was unchanged by phenobarbital and only slightly shifted (−0.8 nm) by 3-methylcholanthrene or β-naphthoflavone treatment. Voles and mice represent different families of the order Rodentia. The results obtained with voles more closely resemble those reported for hamsters which are in the same family but a different subfamily than voles. Comparative consideration of the taxonomic relations of the rodents, therefore, may be useful in interpreting their comparative toxicology.