Genetic toxicity assessment using liver cell models: past, present, and future

Area of Science:

• Toxicology
• Genetic Toxicology
• Cell Biology

Background:

• Standard genotoxicity assays, often using metabolically inactive cells, have high false positive rates.
• Metabolic activation is crucial for understanding pro-carcinogen genotoxicity in vivo.
• Hepatocytes are metabolically active and show promise for predicting in vivo genotoxicity.

Purpose of the Study:

• To review the use of hepatocytes in genotoxicity assessment.
• To summarize findings from standard and novel genotoxicity assays using liver cells.
• To explore advanced liver cell models for improved genetic toxicology.

Main Methods:

• Review of published in vitro and in vivo studies on hepatocyte genotoxicity assessment.
• Description of various liver cell models, including standard and advanced types (3D spheroids, organoids, engineered hepatocytes).
• Summary of findings from different genotoxicity assays.

Main Results:

• Hepatocytes provide a more metabolically relevant model for genotoxicity testing.
• Advanced liver cell models show potential for enhanced prediction of in vivo effects.
• Current in vitro assays often yield high false positive rates due to metabolic incompetence.

Conclusions:

• Hepatocytes are valuable tools for improving the accuracy of genotoxicity risk assessment.
• Advanced liver cell models and integrated strategies enhance biological relevance and throughput.
• A quantitative, human-based cell approach may optimize future genotoxicity testing.