Cadmium induces hypertrophy accompanied by increased myc mRNA accumulation in NRK-49F cells.

Previous studies showed that Cd++ inhibits EGF-induced DNA synthesis but not EGF-induced myc mRNA accumulation or amino acid incorporation into protein in serum-starved NRK-49F cells. In this study, flow cytometry was used to analyze the DNA and protein content of individual cells stimulated with Cd++ and/or epidermal growth factor (EGF). myc oncogene expression in these cells was also measured. It was found that, in both parental NRK-49F cells and in a clonal subpopulation, N1, Cd++ induces an hypertrophic response. In parental NRK-49F cells, however, lower doses of Cd++ (0.5 microM) induced more pronounced hypertrophic responses than did higher doses (4 microM); whereas in N1 cells, the Cd+(+)-induced hypertrophic response shows a pattern of increasing response with doses of Cd++ from 0.5 to 4 microM. myc mRNA accumulation measured 2 hours after stimulation correlated with the hypertrophic responses in both NRK-49F cells and in N1 cells. The results show that Cd+(+)-induced hypertrophy in NRK-49F cells is associated with increased myc oncogene mRNA accumulation, indicating that cell proliferation and cell hypertrophy may in part share common activation pathways.