Chimeric mice with human hepatocytes: A new system for genotoxicity studies

Area of Science:

• Toxicology
• Genetics
• Biomedical Engineering

Background:

• Genotoxicity assays traditionally use various cell types (bacterial, mammalian, rodent) as targets.
• Human cell relevance in genotoxicity testing is crucial for accurate human risk assessment.
• Current in vivo genotoxicity studies predominantly utilize cultured human cells, limiting direct in vivo relevance.

Purpose of the Study:

• To evaluate human hepatocytes within PXB-mice as a suitable in vivo target for genotoxicity assays.
• To assess the utility of PXB-mice for detecting DNA damage and chromosomal aberrations in human liver cells.
• To establish a novel in vivo model for human genotoxicity testing.

Main Methods:

• Utilized PXB-mice, chimeric mice with human hepatocyte repopulation.
• Applied the single-cell gel electrophoresis (comet) assay to detect DNA damage.
• Employed the micronucleus assay to evaluate chromosomal aberrations.

Main Results:

• Demonstrated the feasibility of using human hepatocytes in PXB-mice for genotoxicity testing.
• Successfully detected DNA damage and chromosomal aberrations in the humanized liver cells.
• Validated PXB-mice as a functional model for in vivo genotoxicity assays.

Conclusions:

• PXB-mice provide a valuable in vivo model system for human genotoxicity assays.
• This model enhances the assessment of chemical genotoxicity in human liver cells.
• The approach offers improved relevance for human health risk evaluations.