title: The role of DNA cluster damage and chromosome aberrations in radiation-induced cell killing: a theoretical approach.
abstract: The role played by DNA cluster damage and chromosome aberrations in radiation-induced cell killing was investigated, assuming that certain chromosome aberrations (dicentrics, rings and large deletions, or 'lethal aberrations') lead to clonogenic inactivation and that chromosome aberrations are due to micrometre-scale rejoining of chromosome fragments derived from DNA cluster lesions (CLs). The CL yield and the threshold distance governing fragment rejoining were left as model parameters. The model, implemented as a Monte Carlo code called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations), provided simulated survival curves that were compared with survival data on AG1522 and V79 cells exposed to different radiation types, including heavy ions. The agreement between simulation outcomes and experimental data suggests that lethal aberrations are likely to play an important role in cell killing not only for AG1522 cells exposed to X rays, as already reported by others, but also for other radiation types and other cells. Furthermore, the results are consistent with the hypothesis that the critical DNA lesions leading to cell death and chromosome aberrations are double-strand break clusters (possibly involving the ∼1000-10 000 bp scale) and that the effects of such clusters are modulated by micrometre-scale proximity effects during DNA damage processing.
authors: Department of Physics, University of Pavia, and INFN, Sezione di Pavia, via Bassi 6, Pavia, Italy francesca.ballarini@unipv.it.
authors: F
authors: F
authors: Ballarini
authors: Department of Physics, University of Pavia, and INFN, Sezione di Pavia, via Bassi 6, Pavia, Italy.
authors: S
authors: S
authors: Altieri
authors: Department of Physics, University of Pavia, and INFN, Sezione di Pavia, via Bassi 6, Pavia, Italy.
authors: S
authors: S
authors: Bortolussi
authors: Department of Physics, University of Pavia, and INFN, Sezione di Pavia, via Bassi 6, Pavia, Italy.
authors: M
authors: M
authors: Carante
authors: Department of Physics, University of Pavia, and INFN, Sezione di Pavia, via Bassi 6, Pavia, Italy.
authors: E
authors: E
authors: Giroletti
authors: Department of Physics, University of Pavia, and INFN, Sezione di Pavia, via Bassi 6, Pavia, Italy.
authors: N
authors: N
authors: Protti
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000528:radiation effects*; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000528:radiation effects*; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects*; D006801:Humans; D018499:Linear Energy Transfer / Q000528:radiation effects; D008168:Lung / Q000166:cytology / Q000528:radiation effects*; D008962:Models, Theoretical; D009010:Monte Carlo Method; D011829:Radiation Dosage; D014965:X-Rays