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.