AT Cells Show Dissimilar Hypersensitivity to Heavy-Ion and X-rays Irradiation

Ataxia telangiectasia (AT) cells, with then defective double-strand break (DSB) repair processes. exhibit high sensitivity to low-LET radiation such as X-rays irradiation and gamma beams Since heavy ion beam treatment for cancer is becoming increasingly common in Japan and elsewhere, it is important to also determine their sensitivity to high-LET radiation For this purpose we irradiated AT and normal human cells immortalized with the human telomerase gene using high- (24-60 keV/mu m carbon and 200 keV/mu m iron ions) or low-LET (X-rays) radiation in non-proliferative conditions. In normal cells the RBE (relative biological effectiveness) of carbon and iron ions increased from 1 19 to 1.81 in proportion to LET. In contrast. their RBE in AT cells increased from 1 32 at 24 keV/mu m to 1.59 at 40 keV/mu m, and exhibited a plateau at over 40 keV/mu m. In normal cells most gamma-H2AX foci induced by both carbon- and iron-ion beams had disappeared at 40 h In AT cells. however, a significant number of gamma-H2AX foci were still observed at 40 h. The RBEs found in the AT cells after heavy-ion irradiation were. consistent with the effects predicted from the presence of non-homologous end joining defects. The DSBs remaining after heavy-ion irradiation suggested defects in the AT cells' DSB repair ability.