@misc{oai:repo.qst.go.jp:00059479,
 author = {Furusawa, Yoshiya and Aoki, Mizuho and Utsumi, Hiroshi and Takata, Minoru and Ando, Koichi and 古澤 佳也 and 青木 瑞穂 and 内海 博司 and 安藤 興一},
 month = {Aug},
 note = {It is widely recognized that most radiation-induced biological endpoints are determined by the consequence of the repair of DNA double-strand breaks (dsb).  Despite a large amount of molecular studies, the exact mechanisms underlying DNA repair and its fidelity are not known and remain to be elucidated.  Recently, a series of DNA dsb repair gene knockout chicken cell-lines (DT40) were established.  In the research work described in this paper, we examined the survival curves of the following DT40 lines: ku70-/- (NHEJ; non-homologous end-joining deficient), rad54-/- (HR; homologous recombination deficient), ku70-/-rad54-/- (double deficient), and wild-type DT40 cells. These repair-deficient cell lines were exposed to X-rays and different heavy charged particle beams accelerated with the HIMAC accelerator in Chiba, Japan, covering a LET range 2 - 800 keV/um.  The ku70-/-rad54-/- strain showed the highest radiosensitivity (D10 = 0.68 Gy for X-rays) followed by the rad54-/- strain (2.3 Gy), and subsequently the wild type strain (4.2 Gy).  The ku70-/- strain showed a bi-phasic survival curve.  At low doses, the survival curve was similar to that of the ku70-/-rad54-/- double-knockout strain.  At high dose the curve displayed a pronounced shoulder, reflecting radioresistance at a level even higher than the wild type strain.  The RBEs for the repair sufficient strains (ku70-/- strain at late-S/G2 phase, rad54-/-, and wild strains) showed a typical LET dependence, i.e., RBE increased with LET, showed a peak at around 200 keV/um, and then decreased.  However, the RBE for the repair deficient strains (ku70-/- strain at G1/early-S phase and ku70-/-rad54-/- strain) was approximately constant up to an LET value arond 100 keV/um, and decreased at higher LET values.  The lack of increase at low-LET is probably caused by the inhability to repair, and misrepair, the DNA damage, whereas  the decrease of RBE at higher LET is caused by the decrease of ion hit probability., The First International Symposium on Ion Beams: Biological Effects and Molecular Mechanisms},
 title = {Increase of the RBE with LET after Irradiation of Charged Particle Beams Causes by Misrepair of DNA Double Strand Breaks},
 year = {2002}
}