Effects of nucleoside triphosphates and ferrous ions on bleomycin-induced unscheduled DNA synthesis.
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 triphosphates at 0.2-2.0 mM and 1.5- to 3-fold by addition of ferrous ions at 10 microM. Sensitivity to deferoxamine, a specific iron chelator, suggested that iron was essential to nucleotide-enhanced, bleomycin-induced UDS. Enhancement by nucleotides was not attributed to iron impurities in the nucleotide preparations, because ferrous ions did not substitute for nucleotides, 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.
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Seki
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Ikeda
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Oda
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D051379:Mice; D009711:Nucleotides / Q000494:pharmacology*; D010539:Permeability; D012513:Sarcoma, Experimental / Q000473:pathology
D004273:DNA, Neoplasm; D009711:Nucleotides; D001761:Bleomycin; D007501:Iron