Identification of the molecular basis of doxorubicin-induced cardiotoxicity.

Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Nature medicine (Impact Factor: 28.05). 10/2012; DOI: 10.1038/nm.2919
Source: PubMed

ABSTRACT Doxorubicin is believed to cause dose-dependent cardiotoxicity through redox cycling and the generation of reactive oxygen species (ROS). Here we show that cardiomyocyte-specific deletion of Top2b (encoding topoisomerase-IIβ) protects cardiomyocytes from doxorubicin-induced DNA double-strand breaks and transcriptome changes that are responsible for defective mitochondrial biogenesis and ROS formation. Furthermore, cardiomyocyte-specific deletion of Top2b protects mice from the development of doxorubicin-induced progressive heart failure, suggesting that doxorubicin-induced cardiotoxicity is mediated by topoisomerase-IIβ in cardiomyocytes.

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