Biphenyl hydroxylations and spectrally apparent interactions with liver microsomes from hamsters pre-treated with phenobarbitone and 3-methylcholanthrene.
1. Metabolism of [14-C]biphenyl by hamster liver microsomes has been studied by t.l.c., quantitative fluorimetry and difference absorption spectrophotometry. 2. 4-Hydroxybiphenyl (major metabolite) and 2-hydroxybiphenyl (minor) accounted for at least 83% of total biphenyl metabolism. Small quantities of 2,2'- and 4,4'-dihydroxybiphenyl metabolites were also tentatively identified. 3. Biphenyl 2- and 4-hydroxylations exhibited different NADPH-NADH specificities and pH profiles. 4. Phenobarbitone preferentially induced formation of 4-hydroxybiphenyl, while 3-methylcholanthrene induced 2- and 4-hydroxylation almost equally by affecting both production and further metabolism of 2- and 4-hydroxybiphenyl. 5. Biphenyl, 2- and 4-hydroxy- and 2,2'-dihydroxybiphenyl gave both high- and low-affinity type I spectrally apparent microsomal interactions, whereas 4,4'-dihydroxybiphenyl promoted a reverse type I spectral change. There was an inverse correlation between the spectral dissociation constants (Ks) and lipid solubilities for the low-affinity type I interactions and a possible direct correlation for the high-affinity type I interactions. 6. Phenobarbitone and 3-methylcholanthrene induced cytochrome P-450 and cytochrome P-448 respectively and produced complex changes in the biphenyl type I interaction kinetics. No direct relationship was found in 'control' or 'induced' microsomes between biphenyl 2- or 4-hydroxylation, the type I interaction and cytochrome P-450 concentration. The results are discussed in terms of a 3-methylcholanthrene-inducible biphenyl 2- and 4-hydroxylase and a phenobarbitone-inducible biphenyl 4-hydroxylase.
D000438:Alcohols / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003580:Cytochromes / Q000096:biosynthesis; D006900:Hydroxylation; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*
D000438:Alcohols; D001713:Biphenyl Compounds; D002250:Carbon Radioisotopes; D003580:Cytochromes; D009243:NAD; D009249:NADP; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital