Cd++ inhibits EGF induced DNA synthesis but not EGF induced myc mRNA accumulation in serum starved NRK-49F cells.

Cd++ inhibits EGF-induced 3H-thymidine incorporation in serum deprived NRK-49F cells in a dose dependent pattern. The underlying mechanisms for this inhibition are largely unknown. EGF-induced myc mRNA accumulation in NRK-49F cells and the effects of Cd++ on this response were examined under conditions that result in partial or complete inhibition of EGF-induced DNA synthesis. It was found that doses of Cd++ that inhibit EGF-induced DNA synthesis do not inhibit EGF-induced protein synthesis and myc mRNA accumulation. Cd++ doses of 0.5 microM and 1 microM were found actually to increase EGF-induced myc mRNA accumulation and amino acid incorporation. These results show that the effect of Cd++ on EGF-induced DNA synthesis is not due to inhibition of entrance into G1, but rather that Cd++ acts on events subsequent to myc accumulation; that is, events associated with either G1 progression, entry into S or DNA synthesis.