Abstract
Lymphocyte cultures from all normal human adults are stimulated by zinc ions to increase DNA and RNA synthesis and undergo blast transformation. Optimal stimulation occurs at 0.1 mM Zn(++). Examination of the effects of other divalent cations reveals that 0.01 mM Hg(++) also stimulates lymphocyte DNA synthesis. Ca(++) and Mg(++) do not affect DNA synthesis in this culture system, while Mn(++), Co(++), Cd(++), Cu(++), and Ni(++) at concentrations of 10(-7)-10(-3) M are inhibitory. DNA and RNA synthesis and blast transformation begin to increase after cultures are incubated for 2-3 days with Zn(++) and these processes reach a maximum rate after 6 days. The increase in Zn(++)-stimulated lymphocyte DNA synthesis is prevented by rendering cells incapable of DNA-dependent RNA synthesis with actinomycin D or by blocking protein synthesis with cycloheximide or puromycin. Zn(++)-stimulated DNA synthesis is also partially inhibited by 5'-AMP and chloramphenicol. Zn(++) must be present for the entire 6-day culture period to produce maximum stimulation of DNA synthesis. In contrast to its ability to independently stimulate DNA synthesis, 0.1 mM Zn(++) inhibits DNA synthesis in phytohemagglutinin-stimulated lymphocytes and L1210 lymphoblasts.