title: Mutagenesis in mammalian cells can be modulated by radiation-induced voltage-dependent potassium channels.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Stanford University, CA 94305.
authors.forename: A H
authors.initials: AH
authors.lastname: Saad
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhou
authors.forename: E K
authors.initials: EK
authors.lastname: Lambe
authors.forename: G M
authors.initials: GM
authors.lastname: Hahn
mesh_terms: 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
chemical_list: 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