Mechanism of bleomycin: evidence for a rate-determining 4'-hydrogen abstraction from poly(dA-dU) associated with the formation of both free base and base propenal.

When poly(dA-[4'-3H]dU) was degraded by activated bleomycin under a variety of conditions, 50 +/- 10% of the deoxyuridine residues were converted to uracil and uracil propenal, paralleling observations made with DNA. By manipulation of the concentration of O2 in solution, the relative ratio of uracil propenal to uracil could be varied between 0.03 for anaerobic activation and 7.0 for activation at 3 atm of O2. Tritium selection effects on 4'-hydrogen abstraction were also measured under these conditions and found to range from 7.2 to 12.5. These results strongly suggest that the formation of both uracil and uracil propenal is the consequence of a rate-determining 4'-carbon-hydrogen bond cleavage and of an O2-dependent partitioning of the intermediate produced by this cleavage.