title: AT cells show dissimilar hypersensitivity to heavy-ion and X-rays irradiation.
abstract: Ataxia telangiectasia (AT) cells, with their 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/microm carbon and 200 keV/microm 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/microm to 1.59 at 40 keV/microm, and exhibited a plateau at over 40 keV/microm. 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.
authors.affiliation: Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan .
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kitajima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Adachi
authors.forename: Kei
authors.initials: K
authors.lastname: Ijichi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yasui
authors.forename: Noriko
authors.initials: N
authors.lastname: Saito
authors.forename: Masao
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kurita
authors.forename: Kanji
authors.initials: K
authors.lastname: Ishizaki
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics; D002244:Carbon / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000528:radiation effects; D020450:Heavy Ions; D006657:Histones / Q000378:metabolism; D006801:Humans; D007477:Ions / Q000737:chemistry; D018499:Linear Energy Transfer; D012062:Relative Biological Effectiveness; D019098:Telomerase / Q000235:genetics; D014965:X-Rays
chemical_list: C468783:H2AX protein, human; D006657:Histones; D007477:Ions; D002244:Carbon; D019098:Telomerase