BACKGROUND AND AIM: The clinical use of doxorubicin (DOX) and other 
anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead 
to cardiomyopathy. The role of the individual genetic makeup in this disorder is 
poorly understood. Alterations in genes encoding cardiac cytoskeleton or 
sarcolemma proteins may increase the susceptibility to doxorubicin-related 
cardiotoxicity.
METHODS: Female dystrophin-deficient mice (MDX) and age-matched wild-type mice 
underwent chronic treatment with doxorubicin. Cardiac function and tissue damage 
were assessed by echocardiography and histopathology, respectively. Gene 
expression changes were investigated using microarrays.
RESULTS: DOX treatment resulted in mortality, cardiac insufficiency, and cardiac 
interstitial fibrosis. These alterations were more pronounced in DOX-treated MDX 
mice than in DOX-treated wild-type mice. Changes in gene expression were more 
numerous in MDX mice, including genes involved in cell adhesion, oxidative 
stress, cytoskeleton organization, inflammatory and immune response and cell 
death.
CONCLUSIONS: Dystrophin deficiency facilitates the development and progression 
of doxorubicin-induced cardiac injury. The underlying mechanisms may involve 
changes in cell adhesion, in cytoskeleton, as well as in inflammatory and immune 
responses. Genetic variants of cytoskeletal proteins in humans may affect the 
individual susceptibility to doxorubicin. Cardiotoxic drugs may accelerate the 
manifestation of pre-clinical cardiomyopathies caused by deficiencies in 
cytoskeletal or sarcolemma proteins.