Inhibition of ribonucleotide reductase activity by IC202C.

suppresses DNAsynthesis by inhibition of ribonucleotide reductase.4) Ribonucleotide reductase plays an essential role in DNAsynthesis in most organisms.5) The enzyme is a nonheme iron-containing protein, which requires ATPand Mg2+ as co factors. As previously reported that IC202C has art affinity against Fe(III) ion,3) we have examined the effect of IC202C on ribonucleotide reductase activity using EL4 mouse T lymphoma cells. EL4 cell (7X 107) extracts were prepared as described by Hoffbrand et al.,4) and ribonucleotide reductase activity in the cell extracts was determined according to the method by Thelandar6) and Gleason,5) using [5-3H]cytidine 5 '-diphoshate ammonium salt as a substrate. After the reaction at 37°C for 1 hour, the radioactivity of dCMPwas counted by a liquid scintillation counter. As a result, IC202C significantly inhibited ribonucleotide reductase in EL4 cell extracts in vitro as well as hydroxyurea and deferoxamine (Sigma-Aldrich Japan, Tokyo), typical inhibitors of ribonucleotide reductase (Table 1). IC202C also inhibited the enzyme activity in