A Deletion of Mitochondrial DNA in Murine Doxorubicin-Induced Cardiotoxicity

Biochem Biophys Res Commun. 1993 Sep 15;195(2):945-51. doi: 10.1006/bbrc.1993.2135.

Abstract

A deletion of about 4 kb has been determined in the mutated mitochondrial DNA (mtDNA) in cardiomyocytes with chronic doxorubicin (DOX)-induced cardiotoxicity in mouse. The incidence of the mtDNA deletion increased with the dosage and with the duration of the DOX administration. Coenzyme Q10 administration prevented the mtDNA deletion and decreased the thiobarbituric acid reactive substance content in the heart mitochondria, suggesting some free radical involvement in this mtDNA deletion. This mtDNA deletion may be involved in cardiomyopathy, which is known to be dosage-dependently induced by DOX administration.

MeSH terms

  • Animals
  • Base Sequence
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / isolation & purification
  • Doxorubicin / toxicity*
  • Heart / drug effects*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism*
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • Sequence Deletion*
  • Thiobarbituric Acid Reactive Substances / analysis

Substances

  • DNA, Mitochondrial
  • Oligodeoxyribonucleotides
  • Thiobarbituric Acid Reactive Substances
  • Doxorubicin