title: Repair of potentially lethal damage in normal cells and ataxia telangiectasia cells; consideration of non-homologous end-joining.
abstract: When cell lines are held in a quiescent state after irradiation, survival rates are greater than those from cells that are stimulated to grow immediately after irradiation. These differences in survival rates correspond to rates of potentially lethal damage repair. The effects of confluent holding recovery after gamma-irradiation were investigated using normal human fibroblasts (AG1522) and ataxia telangiectasia fibroblasts (GM02052). Calyculin-A-induced premature chromosome condensation and fluorescent in situ hybridization were applied to study G2/M chromosomal aberrations. Survival results indicated normal capacity for PLDR in AG1522 cells but that PLDR was extremely compromised in GM02052 cells. The chromosomal aberration frequency decreased when AG1522 cells were allowed to repair for 24-h, whereas 24-hour incubation had little effect on the aberration frequency in GM02052 cells. Since the main mechanism for dsbs repair during G0/G1 phases of the cells cycle involve the non-homologous end-joining (NHEJ) process, our study indicates that for AG1522 cells the NHEJ repair process is more likely to induce accurate chromosome repair under quiescent G0 conditions than proliferating G1 phase, while in GM02052 cells the fidelity of NHEJ is similarly defective at either cell cycle phase. Reduced fidelity of NHEJ may be responsible for PLDR defect and its hyper-radiosensitivity in A-T cells.
authors.affiliation: Department of Radiology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Momoe
authors.initials: M
authors.lastname: Kan'o
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawata
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Shigematsu
authors.forename: Cuihua
authors.initials: C
authors.lastname: Liu
authors.forename: Takashi
authors.initials: T
authors.lastname: Uno
authors.forename: Kouich
authors.initials: K
authors.lastname: Isobe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawakami
authors.forename: Francis
authors.initials: F
authors.lastname: Cucinotta
authors.forename: Kerry
authors.initials: K
authors.lastname: George
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kubo
mesh_terms: D001260:Ataxia Telangiectasia / Q000473:pathology* / Q000503:physiopathology*; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D019457:Chromosome Breakage / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans