1 research outputs found
Microsomal Oxidation of 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB 136) Results in Species-Dependent Chiral Signatures of the Hydroxylated Metabolites
Chiral polychlorinated biphenyls
(PCBs) display variable atropisomeric
enrichment in wildlife and animal models, especially at higher trophic
levels. These differences in PCBs’ chiral signatures are, at
least in part, due to species-dependent oxidation of PCBs to hydroxylated
PCB metabolites (OH-PCBs). Here, we investigate the hypothesis that
the cytochrome P450 (P450) enzyme-mediated oxidation of chiral PCBs
results in species-dependent differences in the chiral signatures
of OH-PCBs (i.e., the direction and extent of OH-PCBs’ atropisomeric
enrichment). To investigate this hypothesis, we incubated PCB 136,
a representative chiral PCB, with pooled human liver microsomes (HLMs)
or liver microsomes from male guinea pig, hamster, monkey, mouse,
and rabbit or female dog and determined average profiles and chiral
signatures of the OH-PCBs. 2,2′,3,3′,6,6′-Hexachlorobiphenyl-4-ol
(4–136) was the major metabolite in incubations with HLMs and
monkey and rabbit microsomes. 2,2′,3,3′,6,6′-Hexachlorobiphenyl-5-ol
(5–136) was the major metabolite formed by microsomes from
all other species. Both 4–136 and 5–136 were formed
atropselectively in all microsomal incubations; however, the direction
and extent of the atropisomeric enrichment of both OH-PCB metabolites
showed considerable differences across microsomal preparations obtained
from different species. These differences in OH-PCBs’ atropisomeric
enrichment may not only be toxicologically relevant but may also be
useful to study sources and transport of OH-PCBs in the environment