Effects of iron, copper and zinc on the activity of ribonucleotide reductase in normal and leukemic human lymphocytes.
The activity of ribonucleotide reductase (RR) extracted from normal and leukemic human lymphocytes was assessed. The activity of the enzyme was five times higher in leukemic cells than in normal lymphocytes. Fe and Cu stimulated and Zn inhibited RR activity in both types of cells. Zn also partially reduced the stimulatory effects of Fe and Cu. Deferoxamine (DFX) alone inhibited the activity of the enzyme and enhanced a similar inhibitory action of hydroxyurea (HU). In both cases the inhibitory effects were reversed by Fe and Cu, but not Zn. These findings suggest that: 1) Fe, Cu and Zn may modulate RR activity in vitro and their action is related and interdependent. 2) DFX alone may inhibit RR activity. 3) DFX enhances HU effect on leukemic cells. 4) The effects of both inhibitors may be modified by trace metals.
Oblender
M
M
Pediatric Department, University of Texas Medical Branch, Galveston 77550.
Carpentieri
U
U
D003300:Copper / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D007938:Leukemia / Q000201:enzymology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D012264:Ribonucleotide Reductases / Q000032:analysis* / Q000037:antagonists & inhibitors; D015032:Zinc / Q000494:pharmacology*
D003300:Copper; D007501:Iron; D012264:Ribonucleotide Reductases; D003676:Deferoxamine; D015032:Zinc; D006918:Hydroxyurea