JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Four functional genotoxic marker genes (Bax, Btg2, Ccng1, and Cdkn1a) discriminate genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens and non-genotoxic non-hepatocarcinogens in rat public toxicogenomics data, Open TG-GATEs

  • 0Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-Ku, Kawasaki, Kanagawa, 210-9501, Japan. chiefurihata@gmail.com.
Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society +

|

December 20, 2024

|

December 20, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Four key genes (Bax, Btg2, Ccng1, and Cdkn1a) effectively distinguish genotoxic hepatocarcinogens (GTHCs) from non-genotoxic ones in rat liver toxicogenomics data. This validates their use in future studies for improved carcinogen identification.

Area Of Science

  • Toxicology
  • Genomics
  • Biomarker Discovery

Background

  • Previous studies proposed gene sets to differentiate genotoxic and non-genotoxic hepatocarcinogens (GTHCs/NGTHCs).
  • The Japanese Environmental Mutagen and Genome Society proposed 12 genes, while the US EPA suggested seven, with four common genes identified (Bax, Btg2, Ccng1, Cdkn1a).

Purpose Of The Study

  • To evaluate the performance of the four common genes (Bax, Btg2, Ccng1, Cdkn1a) in discriminating GTHCs from NGTHCs and non-genotoxic non-hepatocarcinogens (NGTNHCs) using Open TG-GATEs data.
  • To confirm the utility of these four genes in rat liver toxicogenomics studies.

Main Methods

  • Utilized principal component analysis (PCA) on the Open TG-GATEs dataset.
  • Analyzed gene expression profiles 24 hours after single administration and after 28-day repeated administrations.

Main Results

  • The four genes achieved 100% accuracy in distinguishing typical GTHCs from NGTHCs and NGTNHCs after single administration.
  • Similar or improved performance was observed in repeated administration studies.
  • Intermediate GTHC/NGTHCs were located in an intermediate region in PCA, suggesting nuanced discrimination.

Conclusions

  • The four genes (Bax, Btg2, Ccng1, Cdkn1a) combined with PCA are effective for discriminating GTHCs from NGTHCs and NGTNHCs in rat liver toxicogenomics data.
  • These genes are recommended for prioritization in future rat liver in vivo toxicogenomics tests for carcinogen identification.

Keywords: