Activated bleomycin is the drug species seen to be kinetically competent to
initiate DNA degradation in the reaction of bleomycin, Fe(II), and O-2 It
also forms in reactions of bleomycin with Fe(III) and peroxide, or bleomyci
n with superoxide and either Fe(III) or Fe(II). Efforts to characterize thi
s transient species proceeded by kinetic and spectroscopic strategies. Acti
vated bleomycin now appears to be a drug-ferric-peroxide complex, but this
may not be the proximate active drug species. Assuming that activated bleom
ycin peroxide cleavage yields a reactive product analogous to peroxidase co
mpound I explains many characteristics of bleomycin-mediated DNA degradatio
n reactions. DNA degradation is responsible for the cytotoxic and antitumor
activities of this clinically useful antibiotic.