MUTAGENESIS IN MAMMALIAN-CELLS CAN BE MODULATED BY RADIATION-INDUCED VOLTAGE-DEPENDENT POTASSIUM CHANNELS

In mammalian cells, little is known about the initial events whose ult imate consequence is mutagenesis or DNA repair. The role the plasma me mbrane may play as an initiator of such a pathway is not understood. W e show, for the first time, that membrane voltage-dependent potassium (K+) currents, activated by ionizing radiation (Kuo et al., 1993), pla y a significant role in radiation mutagenesis. Specifically, we show t hat the frequency of mutation at the HGPRT locus is increased as expec ted to 37.6 +/- 4.0 mutations per 100 000 survivors by 800 cGy of ioni zing radiation from a spontaneous frequency of 1.5 +/- 1.5. This incre ase, however, is abolished if either K+ channel blocker, CsCl or BaCl2 , is present for 2 h following irradiation of the cells. RbCl, chemica lly similar to CsCl but known not to block K+ channels, is ineffective in reducing the mutation frequency. Treatment of cells with CsCl or B aCl2 had no effect on radiation-induced cell killing.