Differential growth-inhibitory effects of gallium on B-lymphocyte lines in high versus low iron concentrations

The growth inhibitory effects of gallium on a murine and human B-cell line were studied using two different serum-free culture systems: (a) ferric citrate medium containing 500 microM iron and (b) transferrin medium containing 5 micrograms/ml of iron-saturated transferrin (0.125 microM iron). For the human cell line in ferric citrate medium, 50% growth inhibition achieved in the presence of transferrin-gallium represented a gallium concentration 80-fold lower than the concentration required when gallium nitrate was added. In the transferrin system, significantly higher transferrin-gallium concentrations were required to achieve the same inhibitory effects. Monoclonal antibody to the transferrin receptor significantly decreased the growth inhibiting effect of transferrin-gallium in the mouse ferric citrate system. Thus, under very different culture conditions, gallium and iron appear to compete via the transferrin-transferrin receptor pathway for cellular uptake. The growth inhibitory effects of gallium are markedly potentiated when the metal is taken up by functional transferrin receptors even in cells continuously cultured in transferrin-free medium.