Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine on the activities of bleomycin to inhibit DNA synthesis and growth of cultured cells.
Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine, which form stable complexes preferentially with Fe(II), Fe(II) and specifically with Cu(I), respectively, on the inhibitory activity of bleomycin against DNA synthesis of rat ascites hepatoma AH66 cells were examined. The inhibitory activity of metal-free bleomycin was suppressed in the presence of o-phenanthroline or 2,2'-dipyridyl, but not by neocuproine, though these chelating agents also showed the inhibitory activity against the DNA synthesis of the cells by themselves alone. The activity of bleomycin-Cu(II) was also suppressed by o-phenanthroline, but bleomycin-Fe(II) and bleomycin-Fe(III) exhibited some activities in the presence of o-phenanthroline. The growth inhibitory activity of bleomycin against HeLa cells was also suppressed by o-phenanthroline. From these results, bleomycin-iron complexes were suggested to be responsible to the bleomycin action in cells.
D015082:2,2'-Dipyridyl / Q000494:pharmacology*; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D010618:Phenanthrolines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats
D004273:DNA, Neoplasm; D010618:Phenanthrolines; D011725:Pyridines; D001761:Bleomycin; C001635:ferroin; D015082:2,2'-Dipyridyl; C002701:neocuproine