4.8 Review

In Vitro Three-Dimensional Liver Models for Nanomaterial DNA Damage Assessment

Journal

SMALL
Volume 17, Issue 15, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202006055

Keywords

adverse outcome pathways; DNA damage; in vitro liver models; long-term exposure; nano(geno)toxicology; nanomaterials

Funding

  1. European Union [760813, 681002]

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This review discusses the chronic liver damage caused by exposure to engineered nanomaterials and the challenges in using in vitro models to assess genotoxicity. It identifies the need for advancements in assessing DNA damage in the liver and highlights the importance of supporting various biochemical endpoints in nano(gen)toxicology research.
Whilst the liver possesses the ability to repair and restore sections of damaged tissue following acute injury, prolonged exposure to engineered nanomaterials (ENM) may induce repetitive injury leading to chronic liver disease. Screening ENM cytotoxicity using 3D liver models has recently been performed, but a significant challenge has been the application of such in vitro models for evaluating ENM associated genotoxicity; a vital component of regulatory human health risk assessment. This review considers the benefits, limitations, and adaptations of specific in vitro approaches to assess DNA damage in the liver, whilst identifying critical advancements required to support a multitude of biochemical endpoints, focusing on nano(geno)toxicology (e.g., secondary genotoxicity, DNA damage, and repair following prolonged or repeated exposures).

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