Stimulatory effect of ascorbate on iron transfer from bleomycin to apotransferrin.

The chemotherapeutic agent, bleomycin, forms a 1:1 complex with both Fe(III) and Fe(II). The rate of ferric ion transfer from bleomycin to apotransferrin is rather slow. However, when ascorbate was added to Fe(III)-bleomycin prior to exposure to apotransferrin, the transfer rate was markedly increased. Ascorbate readily reduces Fe(III)-bleomycin to Fe(II)-bleomycin. A second order rate constant of 2.4 mM-1 min-1 was estimated for this reaction. Fe(II)-bleomycin immediately combines with O2, generating the so-called 'activated bleomycin' complex. The data suggest that a reduced form of iron-bleomycin more readily donates its iron ion to apotransferrin. Reoxidation of ferrous ions, and Fe(III)-transferrin formation occur rapidly.