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Susceptibility to adriamycin-induced hepatotoxicity in mice depends on PRKDC polymorphism

Masaki Watanabe1, Momoka Kakutani1, Ryo Ando2

  • 1Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Aomori, Japan.

The Journal of Veterinary Medical Science
|May 28, 2023
PubMed

Insights

Adriamycin (ADR) chemotherapy causes liver damage, with susceptibility linked to the Prkdc gene

Area of Science:

  • Pharmacology
  • Toxicology
  • Genetics

Background:

  • Adriamycin (ADR) is a vital chemotherapy drug with significant toxicities.
  • ADR-induced liver damage is a clinical concern, yet its mechanisms are not fully elucidated.
  • Rodent models show ADR-induced nephropathy is linked to the Prkdc gene R2140C polymorphism.

Purpose of the Study:

  • To investigate the role of Prkdc gene polymorphism in Adriamycin-induced liver injury.
  • To compare ADR sensitivity across different mouse strains with varying Prkdc genotypes.

Main Methods:

  • Comparative study of ADR-induced liver injury in C57BL/6J (B6J), B6-PrkdcR2140C, and BALB/c mice.
  • Assessment of liver damage and injury markers following ADR administration.

Main Results:

  • C57BL/6J mice demonstrated resistance to ADR-induced liver injury.
  • BALB/c and B6-PrkdcR2140C mice exhibited increased susceptibility to ADR-induced liver damage.
  • The R2140C mutation in the PRKDC gene exacerbated ADR-induced liver injury.

Conclusions:

  • Mouse strain differences and Prkdc polymorphism influence sensitivity to Adriamycin-induced liver damage.
  • The Prkdc R2140C mutation is a key factor in ADR-induced liver susceptibility.
Keywords:
Prkdc geneadriamycinhepatotoxicityliver disease modelmouse

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