ATP significantly enhances degradation of purified viral DNA and DNA in vaccinia cores in the presence of the antineoplastic agent, bleomycin. Thymine has been identified as one of the products of this reaction. Enhancement by ATP of bleomycin-induced degradation of viral DNA requires magnesium chloride and 2-mercaptoethanol; the reaction is dependent on the concentration of bleomycin with maximal degradation occurring at an optimal temperature of 37°. Greatest enhancement is attained when ATP and MgCl2 are present in equimolar concentrations. Increasing the concentration of MgCl2 inhibits degradation in the presence or absence of ATP. Synthetic ATP analogs, α,β-methylene-ATP and β,γ-methylene-ATP, or the nucleotides ADP, GTP, CTP, UTP, dGTP, dCTP and TTP partially substitute for ATP. ATP can not be replaced by AMP, pyrophosphate, 3′,5′-cyclic AMP or EDTA. We suggest that ATP and other nucleotides may be important for bleomycin-induced degradation of DNA observed in intact cells and propose that ATP may play a significant role in the antitumor and antiviral activities of bleomycin.
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