Stimulation of DNA synthesis and 2‐deoxy‐D‐glucose transport in chick embryo cultures by excessive metal concentrations and by a carcinogenic hydrocarbon

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Abstract
Chick embryo cultures deprived of serum synthesize DNA at a reduced rate. DNA synthesis in serum‐deprived cultures is stimulated as much as ten‐fold by the addition of Zn++, Mn++ or Cd++ in concentrations just below the toxic level. These metals, in the same concentration range, also stimulate the uptake of 3H‐2‐deoxy‐D‐glucose (2‐DOG). The increase in uptake of 2‐DOG precedes the increase in synthesis of DNA, and is probably an indicator of a more general membrane perturbation. The metals also stimulate DNA synthesis in serum‐containing, density‐inhibited cultures. The carcinogenic hydrocarbon 9,10‐dimethyl‐1,2‐benzanthracene stimulates DNA synthesis and 2‐DOG uptake in serum‐deprived cultures at those concentrations which also cause morphological changes in the culture. Other carcinogenic hydrocarbons, which produce no morphological changes in the culture do not stimulate DNA synthesis. In contrast to these non‐specific effects, DNA synthesis which is inhibited by low concentrations of either ethylene diamine tetraacetate (EDTA) or diethylene triamine pentaacetate (DTPA) is stimulated specifically by Zn++. These findings are interpreted to mean that certain metals and carcinogens, like a variety of other agents, interact non‐specifically with the plasma membrane to initiate a chain of events leading to DNA synthesis, and that one of these events is the liberation of Zn++ for enzyme reactions leading to DNA synthesis.