Effect of various iron chelating agents on DNA synthesis in human cells

A number of hydroxamic acid derivatives, including salicyl-, octano-, decano- and dodecanohydroxamic acid and rhodotorulic acid, inhibited ³H-thymidine incorporation into DNA, lowered the concentration of dATP and raised the concentration of dTTP in human PHA-stimulated lymphocytes. These effects suggest that these compounds, like desferrioxamine, inhibit ribonucleotide reductase, an iron-requiring enzyme. On the other hand, benzoic acid derivatives did not inhibit ribonucleotide reductase assessed by the dATP and dTTP pool changes, although some did inhibit DNA synthesis judged by ³H-thymidine incorporation into DNA. A number of other compounds known to chelate iron also inhibited DNA synthesis without inhibiting ribonucleotide reductase. These results suggest that different iron binding compounds affect different iron pools in the cell and that some of them may have use as cytotoxic agents.