Effects of zinc deficiency on cellular processes and morphology in Ehrlich ascites tumor cells.

MATERIALS AND METHODS Some biochemical and morphologicaleffects of host zinc deficiency upon Ehrlich cells have been observed and investi gated. The incorporation of [3H]thymidine into DNA of cells from normal and zinc-deficient hosts correlates with the zinc concentration in the ascitic fluid, with incorporation into DNA of zinc-deficient cells considerably depressed compared to cells from animals with adequate dietary zinc intake. Both the uptake of [3Hjthymidine into cells and its subsequent degree of incorporation into DNA are depressed in zinc-deficient tumors. The degree of inhibition correlates with the concentration of zinc in the ascites fluid. In contrast, the incorporation of [3H}. uridine into RNA is much less aftected by zinc-deficient con ditions and, in particular, uptake kinetics are hardly influenced. Furthermore, the kinetics of uptake and incorporation of thy midine into DNA at various fluid zinc concentrations are con sistent with the tumor cell population containing nondividing and normal cycling cells. Cells from zinc-deficient animals respire much more rapidly than do those from normal animals. Other parameters of mitochondrial integrity and regulatory coupling between glycolysis and oxidative phosphorylation are unaffected. A direct control of oxidative phosphorylation by zinc may be involved here. However, electron micrographic analyses of cells from normal and deficient animals show that in severe zinc insufficiency cells show morphological changes consistent with a loss in plasma membrane integrity. Such effects could also cause increased cell respiration.