Proteomics

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Induction of active hepatic cytochrome P450 enzymes in mice exposed to benzo[a]pyrene or environmental mixtures of polycyclic aromatic hydrocarbons


ABSTRACT: Cytochrome P450 enzymes play an important role in bioactivating or detoxifying polycyclic aromatic hydrocarbons (PAHs). We exposed mice to doses of benzo[a]pyrene (BaP) or a mixture of PAHs to characterize dose- and time-response relationships of specific cytochrome P450s. Mice exposed to the highest PAH exposures exhibited 1.7-5-fold higher intrinsic clearance rates for BaP, compared to controls, and higher Vmax values, indicating higher amounts of enzymes capable of metabolizing BaP. This study demonstrates that PAHs induce enzymes in dose- and time-dependent patterns in animal models at exposure levels researchers use to characterize hazards and at relevant human exposure levels to PAH mixtures found at Superfund sites. Accounting for these potential changes in enzyme profiles, relative rates of PAH bioactivation and detoxification, and resulting risk will help reduce uncertainty and improve risk assessments for PAHs at contaminated sites.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Matthew Monroe  

LAB HEAD: Aaron T Wright

PROVIDER: PXD019472 | Pride | 2022-10-13

REPOSITORIES: Pride

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Publications

Exposure to an Environmental Mixture of Polycyclic Aromatic Hydrocarbons Induces Hepatic Cytochrome P450 Enzymes in Mice.

Stoddard Ethan G EG   Nag Subhasree S   Martin Jude J   Tyrrell Kimberly J KJ   Gibbins Teresa T   Anderson Kim A KA   Shukla Anil K AK   Corley Richard R   Wright Aaron T AT   Smith Jordan N JN  

Chemical research in toxicology 20210902 9


Cytochrome P450 enzymes (CYPs) play an important role in bioactivating or detoxifying polycyclic aromatic hydrocarbons (PAHs), common environmental contaminants. While it is widely accepted that exposure to PAHs induces CYPs, effectively increasing rates of xenobiotic metabolism, dose- and time-response patterns of CYP induction are not well-known. In order to better understand dose- and time-response relationships of individual CYPs following induction, we exposed B6129SF1/J mice to single or r  ...[more]

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