RT Journal Article
SR Electronic
T1 2,2',5,5'-Tetrachlorobiphenyl: isolation and identification of metabolites generated by rat liver microsomes.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 197
OP 204
VO 8
IS 4
A1 B D Preston
A1 J R Allen
YR 1980
UL http://dmd.aspetjournals.org/content/8/4/197.abstract
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 microscomes. 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 metablite, 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 two 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.