title: Comparison of the repair of potentially lethal damage after low- and high-LET radiation exposure, assessed from the kinetics and fidelity of chromosome rejoining in normal human fibroblasts.
abstract: Potentially lethal damage (PLD) and its repair (PLDR) were studied in confluent human fibroblasts by analyzing the kinetics of chromosome break rejoining after X-ray or heavy-ion exposures. Cells were either held in the non-cycling G0 phase of the cell cycle for 12 h, or forced to proliferate immediately after irradiation. Fusion premature chromosome condensation (PCC) was combined with fluorescence in situ hybridization (FISH) to study chromosomal aberrations in interphase. The culture condition had no impact on the rejoining kinetics of PCC breaks during the 12 h after X-ray or heavy-ion irradiation. However, 12 h after X-ray and silicon irradiation, cycling cells had more chromosome exchanges than non-cycling cells. After 6 Gy X-rays, the yield of exchanges in cycling cells was 2.8 times higher than that in non-cycling cells, and after 2 Gy of 55 keV/μm silicon ions the yield of exchanges in cycling cells was twice that of non-cycling cells. In contrast, after exposure to 2 Gy 200-keV/μm or 440-keV/μm iron ions the yield of exchanges was similar in non-cycling and cycling cells. Since the majority of repair in G0/G1 occurs via the non-homologous end joining process (NHEJ), increased PLDR in X-ray and silicon-ion irradiated cells may result from improved cell cycle-specific rejoining fidelity through the NHEJ pathway, which is not the case in high-LET iron-ion irradiated cells.
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Liu
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawata
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhou
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kota
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kumabe
authors.forename: Shinya
authors.initials: S
authors.lastname: Sutani
authors.forename: Junichi
authors.initials: J
authors.lastname: Fukada
authors.forename: Masayo
authors.initials: M
authors.lastname: Mishima
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Shigematsu
authors.forename: Kerry
authors.initials: K
authors.lastname: George
authors.forename: Francis
authors.initials: F
authors.lastname: Cucinotta
mesh_terms: D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D002453:Cell Cycle / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects*; D059766:DNA End-Joining Repair / Q000235:genetics* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D018499:Linear Energy Transfer / Q000235:genetics / Q000528:radiation effects*; D011829:Radiation Dosage
keywords: FISH (fluorescence in situ hybridization); PLDR (potentially lethal damage repair); heavy ion; misrepair; premature chromosome condensation