The effect of cyanomorpholinyldoxorubicin, morpholinyldoxorubicin, doxorubicin, 
and Actinomycin D were studied on purified mouse leukemia (L1210) DNA 
topoisomerases I and II. DNA unwinding and cross-linking were also studied. It 
was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and 
Actinomycin D (but not doxorubicin) stimulated DNA topoisomerase I-induced 
cleavage at specific DNA sites; 2) only doxorubicin and Actinomycin D stimulated 
DNA cleavage by DNA topoisomerase II; 3) at higher drug concentrations, DNA 
intercalators suppressed enzyme-mediated DNA cleavage induced by DNA 
topoisomerase I, as well as topoisomerase II; 4) only 
cyanomorpholinyldoxorubicin produced DNA-DNA cross-links; no DNA unwinding could 
be observed; and 5) DNA intercalation (unwinding) potency of 
morpholinyldoxorubicin was about 2-fold less than that of doxorubicin. The data 
indicate that some DNA intercalators are not only inhibitors of DNA 
topoisomerase II but act also on DNA topoisomerase I. The stabilization of 
cleavage intermediates by intercalators may have a common mechanism for DNA 
topoisomerase I and DNA topoisomerase II.