10.1021/acs.est.5b03890.s001
Jean Yoo
Jean
Yoo
Masashi Hirano
Masashi
Hirano
Hazuki Mizukawa
Hazuki
Mizukawa
Kei Nomiyama
Kei
Nomiyama
Tetsuro Agusa
Tetsuro
Agusa
Eun-Young Kim
Eun-Young
Kim
Shinsuke Tanabe
Shinsuke
Tanabe
Hisato Iwata
Hisato
Iwata
In
Vitro and in Silico Analyses for Predicting Hepatic
Cytochrome P450-Dependent Metabolic Potencies of Polychlorinated Biphenyls
in the Baikal Seal
American Chemical Society
2015
Baikal seals
Baikal SealThe aim
CB 22
2 B
chlorine number
Polychlorinated Biphenyls
Baikal seal
heme Fe
Silico Analyses
component analysis
Pusa sibirica
CB 77
PCB ratio
hydroxylated PCBs
liver microsomes
CYP 2A
physicochemical properties
Statistical analysis
cytochrome P 450
62 PCB congener mixtures
polychlorinated biphenyls
2015-12-15 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/In_Vitro_and_in_Silico_Analyses_for_Predicting_Hepatic_Cytochrome_P450_Dependent_Metabolic_Potencies_of_Polychlorinated_Biphenyls_in_the_Baikal_Seal/2099479
The aim of this study was to understand
the cytochrome P450 (CYP)-dependent
metabolic pathway and potency of polychlorinated biphenyls (PCBs)
in the Baikal seal (Pusa sibirica).
In vitro metabolism of 62 PCB congener mixtures was investigated by
using liver microsomes of this species. A decreased ratio of over
20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54,
CB77, and CB105, suggesting the preferential metabolism of low-chlorinated
PCBs by CYPs. The highly activated metabolic pathways in Baikal seals
that were predicted from the decreased PCBs and detected hydroxylated
PCBs (OH-PCBs) were CB22 to 4′OH-CB20 and CB77 to 4′OH-CB79.
The total amount of OH-PCBs detected as identified and unidentified
congeners accounted for only a 3.8 ± 1.7 mol % of loaded PCBs,
indicating many unknown PCB metabolic pathways. To explore factors
involved in CYP-dependent PCB metabolism, we examined the relationships
among the structural and physicochemical properties of PCBs, the in
silico PCB-CYP docking parameters, and the in vitro PCB decreased
ratios by principal component analysis. Statistical analysis showed
that the decreased PCB ratio was at least partly accounted for by
the substituted chlorine number of PCBs and the distance from the
Cl-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and
2B.