Effects of nucleoside triphosphates and ferrous ions on bleomycin-induced unscheduled DNA synthesis

Abstract

Bleomycin-induced, unscheduled DNA synthesis (UDS) in Triton X-100-permeabilized mouse ascites sarcoma cells was enhanced 2- to 5-fold by addition of ribonucleoside triphos-phates at 0.2/emdash 2.0 mM and 1.5- to 3-fold by addition of ferrous ions at 10 μM. Sensitivity to deferoxamine, a specific iron chelator, suggested that iron was essential to nudeotide-enhanced, bleomycin-induced UDS. Enhancement by nucleo-tides was not attributed to iron impurities in the nucleotide preparations, because ferrous ions did not substitute for nu-deotides, but nucleotides further enhanced bleomycin-induced UDS which was maximally stimulated by the optimal concentration of ferrous ions. The effects of nucleotides and ferrous ions on bleomycin-induced UDS were thought to be due to increased bleomycin-induced DNA damage rather than enhanced DNA synthesis. The results suggest that pharmacological action of bleomycin is affected by the concentrations of nucleotides as well as ferrous ions.