Use of a non-hepatic cell line highlights limitations associated with cell-based assessment of metabolically induced toxicity:

Weyers, Carli; Dingle, Laura M K; Wilhelmi, Brendan S; Edkins, Adrienne L; Veale, Clinton G L

Title: Use of a non-hepatic cell line highlights limitations associated with cell-based assessment of metabolically induced toxicity:
Creator: Weyers, Carli, Dingle, Laura M K, Wilhelmi, Brendan S, Edkins, Adrienne L, Veale, Clinton G L
Date: 2020
Type: text
Type: article
Identifier: http://hdl.handle.net/10962/160290
Identifier: vital:40431
Identifier: DOI: 10.1080/01480545.2019.1585869
Description: Metabolically induced drug-toxicity is a major cause of drug failure late in drug optimization phases. Accordingly, in vitro metabolic profiling of compounds is being introduced at earlier stages of the drug discovery pipeline. An increasingly common method to obtain these profiles is through overexpression of key CYP450 metabolic enzymes in immortalized liver cells, to generate competent hepatocyte surrogates. Enhanced cytotoxicity is presumed to be due to toxic metabolite production via the overexpressed enzyme. However, metabolically induced toxicity is a complex multi-parameter phenomenon and the potential background contribution to metabolism arising from the use of liver cells which endogenously express CYP450 isoforms is consistently overlooked. In this study, we sought to reduce the potential background interference by applying this methodology in kidney-derived HEK293 cells which lack endogenous CYP450 expression.
Format: 7 pages, pdf
Language: English
Relation: Drug and chemical toxicology, Weyers, C., Dingle, L.M., Wilhelmi, B.S., Edkins, A.L. and Veale, C.G., 2020. Use of a non-hepatic cell line highlights limitations associated with cell-based assessment of metabolically induced toxicity. Drug and chemical toxicology, 43(6), pp.656-662, Drug and chemical toxicology volume 43 number 6 656 662 2020 1525-6014
Rights: Publisher
Rights: Use of this resource is governed by the terms and conditions of the Taylor and Francis Online Terms and Conditions Statement (https://www.tandfonline.com/terms-and-conditions)

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RU DST/NRF SARChI for Molecular and Cellular Biology of the Eukaryotic Stress Response

Edkins, Adrienne Lesley (Associate Prof)

Wilhelmi, Brendan (Dr)

RU Department of Pharmacy

RU Department of Biochemistry, Microbiology and Bioinformatics

SDG 03. Good Health and Well-Being

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