10.1021/es504766p.s001
Xianai Wu
Xianai
Wu
Christopher Barnhart
Christopher
Barnhart
Pamela
J. Lein
Pamela
J.
Lein
Hans-Joachim Lehmler
Hans-Joachim
Lehmler
Hepatic
Metabolism Affects the Atropselective Disposition
of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136)
in Mice
American Chemical Society
2015
PCB metabolite excretion
WT mice
excreta 3 days
eluting PCB 136 atropisomers
eluting atropisomers
chiral signatures
cytochrome P 450 oxidoreductase
Hepatic Metabolism Affects
extrahepatic cytochrome P 450
PCB 136 tissue levels
hepatic vs extrahepatic metabolism
KO mice
2015-12-17 06:46:03
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Hepatic_Metabolism_Affects_the_Atropselective_Disposition_of_2_2_3_3_6_6_Hexachlorobiphenyl_PCB_136_in_Mice/2046651
To understand the role of hepatic
vs extrahepatic metabolism in
the disposition of chiral PCBs, we studied the disposition of 2,2′,3,3′,6,6′-hexachlorobiphenyl
(PCB 136) and its hydroxylated metabolites (HO-PCBs) in mice with
defective hepatic metabolism due to the liver-specific deletion of
cytochrome P450 oxidoreductase (KO mice). Female KO and congenic wild
type (WT) mice were treated with racemic PCB 136, and levels and chiral
signatures of PCB 136 and HO-PCBs were determined in tissues and excreta
3 days after PCB administration. PCB 136 tissue levels were higher
in KO compared to WT mice. Feces was a major route of PCB metabolite
excretion, with 2,2′,3,3′,6,6′-hexachlorobiphenyl-5-ol
being the major metabolite recovered from feces. (+)-PCB 136, the
second eluting PCB 136 atropisomers, was enriched in all tissues and
excreta. The second eluting atropisomers of the HO-PCBs metabolites
were enriched in blood and liver; 2,2′,3,3′,6,6′-hexachlorobiphenyl-5-ol
in blood was an exception and displayed an enrichment of the first
eluting atropisomers. Fecal HO-PCB levels and chiral signatures changed
with time and differed between KO and WT mice, with larger HO-PCB
enantiomeric fractions in WT compared to KO mice. Our results demonstrate
that hepatic and, possibly, extrahepatic cytochrome P450 (P450) enzymes
play a role in the disposition of PCBs.