In Vitro Metabolism and p53 Activation of Genotoxic Chemicals: Abiotic CYP Enzyme vs Liver Microsomes.

ABSTRACT: Chemicals often require metabolic activation to become genotoxic. Established test guidelines recommend the use of the rat liver S9 fraction or microsomes to introduce metabolic competence to in vitro cell-based bioassays, but the use of animal-derived components in cell culture raises ethical concerns and may lead to quality issues and reproducibility problems. The aim of the present study was to compare the metabolic activation of cyclophosphamide (CPA) and benzo[a]pyrene (BaP) by induced rat liver microsomes and an abiotic cytochrome P450 (CYP) enzyme based on a biomimetic porphyrine catalyst. For the detection of genotoxic effects, the chemicals were tested in a reporter gene assay targeting the activation of the cellular tumor protein p53. Both chemicals were metabolized

SUBMITTER: Henneberger L 

PROVIDER: S-EPMC11337206 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature