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3D Liver Models for Genotoxicity Testing.

Gillian E Conway1, Ume-Kulsoom Shah1, Michael J Burgum1

  • 1In Vitro Toxicology Group, Institute of Life Science, Swansea University Medical School, Swansea, Wales, UK.

Methods in Molecular Biology (Clifton, N.J.)
|November 22, 2025
PubMed
Summary

New 3D liver models offer advanced in vitro genotoxicity testing, supporting the 3Rs (replacement, reduction, refinement) of animal testing. These models accurately assess DNA damage, crucial for product safety and cancer risk evaluation.

Keywords:
3D modelsDNA damageLiver cellMicronucleusMutationNew approach methodologies

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Area of Science:

  • Toxicology
  • Cell Biology
  • Biotechnology

Background:

  • Genotoxicity testing is essential for evaluating new product safety, assessing DNA damage potential linked to cancer risk.
  • The 3Rs (replacement, reduction, refinement) initiative promotes in vitro methods, including New Approach Methodologies (NAMs), to reduce animal testing.
  • 3D human tissue models, particularly liver models, are valuable for in vitro studies due to their enhanced expression of liver-specific enzymes compared to 2D cultures.

Purpose of the Study:

  • To present detailed methodologies for genotoxicity testing using 3D liver cell models.
  • To adapt the micronucleus assay for use with 3D liver models for DNA damage assessment.
  • To explore modifications for nanomaterial assessment and other applications of these 3D liver models.

Main Methods:

  • Utilized 3D liver cell models to investigate DNA damage induction.
  • Employed the micronucleus assay, a standard genotoxicity test, within the 3D liver model system.
  • Developed and refined protocols for applying these methods to assess genotoxicity, including for nanomaterials.

Main Results:

  • Demonstrated the successful application of the micronucleus assay in 3D liver models for genotoxicity testing.
  • Showcased the utility of 3D liver models in recapitulating human liver physiology for in vitro safety assessments.
  • Provided insights into method adaptations for specific applications like nanomaterial testing.

Conclusions:

  • 3D liver cell models provide a more physiologically relevant platform for in vitro genotoxicity testing.
  • These advanced in vitro models support the 3Rs by offering a viable alternative to animal testing for safety assessments.
  • The presented methodologies enable robust DNA damage assessment, contributing to the development of safer products.