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.
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D003956:Dialysis; D004492:Edetic Acid / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
D003470:Culture Media; D002104:Cadmium; D004247:DNA; D003847:Deoxyglucose; D004492:Edetic Acid; D008628:Mercury; D015032:Zinc; D013936:Thymidine; D014529:Uridine