Inhibition of radiation-induced DNA-double strand break repair by various metal/metalloid compounds

Abstract

In order to clarify the mechanism underlying the combined effects of radiation and metals, we have studied the cytotoxicity and inhibition of radiation-induced DNA double-strand-break (DNA-DSB) repair by various metals and metalloids. CHO cells were treated with NiCl 2, NaAsO 2, ZnCl 2, CdCl 2, CuCl 2, and potassium antimonyl tartrate for 2 h, and irradiated with γ-rays at a dose of 40 Gy to induce DNA-DSB. Then, the degree of DNA-DSB was determined by an electrophoresis technique immediately after irradiation and following a 30-min repair period. The DNA-DSB repair was significantly inhibited by exposure to Ni, Cu, Zn, As, Sb, and Cd compounds at concentrations of 200, 2.0, 0.4, 0.08, 0.55, and 1.0 mM, respectively. At these concentrations, the cell viability determined by trypan blue dye exclusion was over 50% for all the chemicals, suggesting that all of these compounds inhibited the repair of radiation-induced DNA-DSB at the concentrations where the acute cytotoxicity was relatively low. More significantly, the plating efficiencies for As, Sb, and Zn compounds at these concentrations were higher than 10%, suggesting that these chemicals inhibited DNA-DSB repair at relatively low concentrations where some of the cells sustained the ability of proliferation.