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

J Vet Med Sci. 2023 Jul 1;85(7):702-704. doi: 10.1292/jvms.23-0115. Epub 2023 May 29.

Abstract

Adriamycin (ADR) is an effective chemotherapy drug for various cancers but has serious side effects. ADR-induced liver damage is a common problem during therapy, but the underlying mechanism remains to be fully understood. In contrast, ADR-induced glomerular damage is well studied in rodents, and sensitivity to ADR-induced nephropathy is because of the R2140C polymorphism of Prkdc gene. To investigate whether strain differences or sensitivity to ADR-induced liver damage are related to Prkdc polymorphism, this study compared the sensitivity to ADR-induced liver damage among C57BL/6J (B6J), B6-PrkdcR2140C, and BALB/c mice. Although B6J exhibits resistance to ADR-induced liver injury, BALB/c and B6-PrkdcR2140C are more susceptible to liver injury, which is exacerbated by the presence of R2140C mutation in PRKDC.

Keywords: Prkdc gene; adriamycin; hepatotoxicity; liver disease model; mouse.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury* / genetics
  • Chemical and Drug Induced Liver Injury* / veterinary
  • Doxorubicin / toxicity
  • Kidney Diseases* / chemically induced
  • Kidney Diseases* / veterinary
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Polymorphism, Genetic

Substances

  • Doxorubicin