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.

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