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 ultimate consequence is mutagenesis or DNA repair. The role the plasma membrane may play as an initiator of such a pathway is not understood. We show, for the first time, that membrane voltage-dependent potassium (K+) currents, activated by ionizing radiation (Kuo et al., 1993), play a significant role in radiation mutagenesis. Specifically, we show that the frequency of mutation at the HGPRT locus is increased as expected to 37.6 +/- 4.0 mutations per 100,000 survivors by 800 cGy of ionizing radiation from a spontaneous frequency of 1.5 +/- 1.5. This increase, however, is abolished if either K+ channel blocker, CsCl or BaCl2, is present for 2 h following irradiation of the cells. RbCl, chemically similar to CsCl but known not to block K+ channels, is ineffective in reducing the mutation frequency. Treatment of cells with CsCl or BaCl2 had no effect on radiation-induced cell killing.
Saad
A H
AH
Department of Radiation Oncology, Stanford University, CA 94305.
Zhou
L Y
LY
Lambe
E K
EK
Hahn
G M
GM
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D016466:CHO Cells; D002586:Cesium / Q000494:pharmacology; D002588:Cesium Radioisotopes; D002712:Chlorides / Q000494:pharmacology; D006224:Cricetinae; D004307:Dose-Response Relationship, Radiation; D004553:Electric Conductivity; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D016296:Mutagenesis; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000528:radiation effects; D011837:Radiation-Protective Agents; D012413:Rubidium / Q000494:pharmacology
D017609:Barium Compounds; D002588:Cesium Radioisotopes; D002712:Chlorides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011837:Radiation-Protective Agents; C024986:barium chloride; D002586:Cesium; D007041:Hypoxanthine Phosphoribosyltransferase; C028019:cesium chloride; D012413:Rubidium; C032710:rubidium chloride