The synergistic action of the copper chelator bathocuproine sulphonate and cysteine in enhancing growth of L1210 cells in vitro.

The growth stimulating effect of a copper-specific chelator, 2,9-dimethyl-4,7-diphenyl-1,10-phenonthroline-sulfonic acid on mouse lymphoma L1210 cells in vitro has been studied. Since they are defective in cystine transport, these cells require cysteine for their growth in vitro. However, addition of cysteine does not greatly enhance cell growth because it is rapidly oxidized to cystine. We have observed that the copper chelator potently inhibited oxidation of cysteine in culture medium and that simultaneous addition of cysteine and the chelator greatly enhanced cell growth. The chelator alone stimulated cell growth slightly by stabilizing a small amount of cysteine effluxed from the cells to the medium. The chelator also enhanced the growth promoting activity of 2-mercaptoethanol by stabilizing cysteine produced in the medium during culture. These results suggest that the chelator stimulates cell growth by inhibiting copper mediated oxidation of cysteine in culture medium.