Control of the growth of leukemic cells (L1210) through manipulation of trace metals.

Trace metals have a role in the activity of the enzyme ribonucleotide reductase (RR) which is essential for the synthesis of DNA and the growth of lymphocytes. Manipulation of the intracellular metals of leukemic cells has been proposed for the therapeutic control of cell growth. We studied the effects of prolonged metal deprivation (Fe, Cu, Zn) on cell growth and RR activity of murine leukemic lymphocytes in culture in metal-depleted media.

Growth, ribonucleotide reductase and metals in murine leukemic lymphocytes.

Trace metals are essential for the growth and several other properties of human lymphocytes. We studied the effects of media with variable concentrations of three metals (Fe2+, Cu2+, Zn2+), a metal chelator (deferoxamine, DFX) and a cell-growth inhibitor (hydroxyurea) on the growth, intracellular metal concentration and activity of the enzyme ribonucleotide reductase in murine leukemic lymphocytes (L1210). Intracellular concentrations of Fe and Cu fluctuated within narrow limits in normal media, but decreased to very low concentrations in metal-poor media.

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.

Trace metals, surface receptors and growth of human normal and leukemic lymphocytes.

To evaluate the modulatory effects of trace metals on lymphocyte growth and maturation, thymidine uptake (TU), protein, ATP, Fe, Cu, Zn, ferritin, CD3, CD4, CD8 antigens, surface transferrin receptors (TFR) and interleukin 2 receptors (IL2R) were assessed in normal and T cell leukemia human lymphocytes, cultured in media with varying Fe, Cu and Zn concentrations [Me]. In normal lymphocytes in media with optimal [Me], all values increased significantly after PHA stimulation, except for intracellular metal concentration and CD3+, CD4+, CD8+ cells which were unchanged. In media with low or high [Me], all parameters except for CD8+ cells were decreased.

Effects of iron, copper, zinc, calcium, and magnesium on human lymphocytes in culture.

The effects of simultaneous changes of calcium, magnesium, iron, copper, and zinc concentrations were evaluated in normal human T and B lymphocytes, cultured in cation-depleted media. Optimal concentrations for thymidine incorporation (TI) in both cell populations were Fe and Zn 15 microM and Cu 5 microM; for T cells Ca 2 mM and Mg 4 mM; for B cells Ca 4 mM and Mg 6 mM. TI decreased with increasing molarity of cations and the decrease was particularly apparent with Cu.