New insight into the mechanism of base propenal formation during bleomycin-mediated DNA degradation

The mechanism of interaction of the antitumor antibiotic bleomycin (BLM) and cofactors with DNA to produce base propenal and 3'-phosphoglycolate and 5'-phosphate ends has been investigated. Analytical methods have been developed that allow the isolation of glycolic acid from the modified DNA without washout of isotopic labels. Results using 18 O 2 , H 2 18 O, and H 2 18 O 2 under a variety of conditions show that 1 mol of 18 O is found per mole of glycolate in the carboxylate group and is derived from the 18 O 2 not used in the formation of activated BLM. The second oxygen in the carboxylate of glycolate is derived from the 4-oxygen in the deoxyribose moiety from which it is generated