Inhibition of Ribonucleotide ReducÃ-aseby Gallium in Murine Leukemic LI 210 Cells1
نویسندگان
چکیده
Our previous studies of the mechanism of cell growth inhibition by gallium have suggested that the block in cellular iron uptake induced by transferrin-gallium results in an inhibition of the iron-dependent M2 subunit of ribonucleotide reducÃ-ase.However, it is not known whether the inhibitory effect of gallium on ribonucleotide reducÃ-aseis solely the result of limiting iron availability for enzyme activity or whether a direct effect of intracellular gallium on the enzyme is also involved. In the present study, utilizing a cell-free assay, we show that gallium nitrate directly inhibits CDP and ADP reducÃ-aseactivity. Inhibition of DNA synthesis by gallium nitrate thus appears to be due to a combination of a block in iron availability to ribonucleotide reducÃ-aseand a direct inhibi tion of the enzyme by gallium.
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