Anthracyclines are active clinical agents that have multiple mechanisms of 
cytotoxicity. Cardiotoxicity by anthracyclines limits the therapeutic potential 
of these agents, but mechanisms leading to cardiotoxicity remain controversial. 
Transgenic mice that lack mitochondrial topoisomerase I are hypersensitive to 
doxorubicin cardiotoxicity, providing support for cardiotoxicity arising from 
damage of mitochondrial DNA.