Binding specificity of chemically and enzymatically activated anthracycline anticancer agents to nucleic acids.

Partial reduction of the quinone containing anticancer drugs, adriamycin and daunorubicin, generated semiquinone intermediates. Incubation of these intermediates with DNA in vitro resulted in covalent binding. The activated adriamycin has a greater binding affinity for nucleic acids, than the daunorubicin intermediate. This covalent binding reaction is essentially complete in 0.5 h. Studies with synthetic polynucleotides have shown a very high preference for poly(dG); however, poly(dC) is also an excellent substrate. Polymers containing either poly(dA) or poly(dT) showed lesser binding. Activation of adriamycin and daunorubicin by microsomes and NADPH also resulted in covalent binding to DNA with identical binding affinities. Longer incubation of these drugs with microsomes decreased binding. This binding is also decreased by Mg2+.