Nonspecific nature of the stimulus to DNA synthesis in cultures of chick embryo cells.

The rate of DNA synthesis in chick embryo cultures deprived of serum is stimulated 5- to 20-fold by a large variety of substances, including subtoxic concentrations of certain metal ions such as Zn++, Cd++, and Hg++. The stimulatory concentrations of Zn++ and Cd++ have sharp optima, which are just below the concentrations that produce frank morphological damage in each case. A much wider gap exists between stimulatory and morphologically damaging concentrations of Hg++. These metal ions also stimulate RNA synthesis, and the uptake of 2-deoxy-D-glucose. The stimulatory effects of Zn++, but not those of Hg++, are prevented by treatment with EDTA. Although medium from cultures stimulated by Zn++ or Hg++ retains its stimulatory capacity for a new set of cultures, the capacity in the case of Zn++-treated cultures is almost entirely lost upon addition of EDTA. It is also lost upon dialysis of conditioned medium from cultures treated with either Zn++ or Hg++. It is concluded that the stimulatory effect is the direct result of interaction between metal ions and cells, and not to the release of growth-stimulatory materials from the cells. The stimulation is thus seen as a non-specific event resulting in an integrated, metabolic response by the cells.