TY - JOUR
T1 - 2,2',5,5'-tetrachlorobiphenyl
T2 - Isolation and identification of metabolites generated by rat liver microsomes
AU - Preston, B. D.
AU - Allen, J. R.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1980
Y1 - 1980
N2 - The in vitro metabolism of 2,2',5,5'-tetrachloro[3H]biphenyl (TCB) by control and phenobarbital-induced rat liver microsomes has been investigated. Phenobarbital induction was found to significantly increase (30-fold) the NADPH-dependent, microsomal metabolism of TCB above that observed with control microsomes. The metabolites generated by microsomes of phenobarbital induced rats were separated by Sephadex LH-20 and gas-liquid chromatography (GLC) and were subsequently characterized by infrared and mass spectral (MS) analyses and techniques of catalytic dechlorination with GLC/MS comparison to biphenylol standards. The major metabolite, representing 90% of all metabolic products, was identified as 3-hydroxy-TCB. 3,4-Dihydro-3,4-dihydroxy-TCB was identified as a minor metabolite (5%), and trace amounts of 2 chromatographically and spectrally distinct dihydroxy-TCB's (4% and 1%) were also found. This in vitro metabolic profile is consistent with that found in vivo and suggests a mechanism of TCB metabolism incorporating both direct hydroxylation and an arene oxide intermediate.
AB - The in vitro metabolism of 2,2',5,5'-tetrachloro[3H]biphenyl (TCB) by control and phenobarbital-induced rat liver microsomes has been investigated. Phenobarbital induction was found to significantly increase (30-fold) the NADPH-dependent, microsomal metabolism of TCB above that observed with control microsomes. The metabolites generated by microsomes of phenobarbital induced rats were separated by Sephadex LH-20 and gas-liquid chromatography (GLC) and were subsequently characterized by infrared and mass spectral (MS) analyses and techniques of catalytic dechlorination with GLC/MS comparison to biphenylol standards. The major metabolite, representing 90% of all metabolic products, was identified as 3-hydroxy-TCB. 3,4-Dihydro-3,4-dihydroxy-TCB was identified as a minor metabolite (5%), and trace amounts of 2 chromatographically and spectrally distinct dihydroxy-TCB's (4% and 1%) were also found. This in vitro metabolic profile is consistent with that found in vivo and suggests a mechanism of TCB metabolism incorporating both direct hydroxylation and an arene oxide intermediate.
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M3 - Article
C2 - 6105050
AN - SCOPUS:0018971795
SN - 0090-9556
VL - 8
SP - 197
EP - 204
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 4
ER -