Human neutrophils exposed to 10(-4) M doxorubicin and the derivatives epirubicin 
and thepirubicin revealed a different intracellular penetration and distribution 
pattern as demonstrated by fluorescence microscopy and fluorimetric 
determination of drug intracellular concentration. While doxorubicin was found 
to be a potent inducer of superoxide generation from resting cells, epirubicin 
exhibited less superoxide-inducing power. Thepirubicin on the contrary did not 
show any superoxide-inducing effect. Moreover the anthracyclines tested all 
inhibited the phorbol ester-stimulated chemiluminescent response to the same 
extent, which suggested a common target for the drug action. 
Anthracycline-stimulated superoxide production seems to correlate with the 
cardiotoxic effects. The most cardiotoxic drug, doxorubicin, is the most potent 
inducer of superoxide generation, while epirubicin, which is less cardiotoxic, 
has a relatively limited effect on superoxide production. Thepirubicin which has 
been shown not to induce delayed cardiomyopathy has no effect on superoxide 
release from the cells.