Exploration of xenobiotic metabolism within cell lines used for Tox21 chemical screening.

ABSTRACT: The Tox21 Program has investigated thousands of chemicals with high-throughput screening assays using cell-based assays to link thousands of chemicals to individual molecular targets/pathways. However, these systems have been widely criticized for their suspected lack of 'metabolic competence' to bioactivate or detoxify chemical exposures. In this study, 9 cell line backgrounds used in Tox21 assays (i.e., HepG2, HEK293, Hela, HCT116, ME180, CHO-K1, GH3.TRE-Luc, C3H10T1/2 and MCF7) were evaluated via metabolite formation rates, along with metabolic clearance and metabolite profiling for HepG2, HEK293, and MCF-7aroERE, in comparison to pooled donor (50) suspensions of primary human hepatocytes (PHHs). Using prototype clinical drug substrates for CYP1A2, CYP2B6, and CYP3A4/5, extremely low-to

SUBMITTER: Qu W 

PROVIDER: S-EPMC10838150 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature