A mechanism-based model of radiation cell death will be presented, assuming that dicentrics, rings and large deletions (“lethal aberrations” or LA) lead to clonogenic inactivation, and that chromosome aberrations derive from DNA cluster lesions (CL) interacting at the m scale. The CL yield and the threshold distance governing chromosome free-end rejoining are the only model parameters. The model, implemented as a MC code called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations), was applied to AG1522 and V79 cells exposed to photons, alpha particles and heavy ions including Carbon. The agreement with data taken from the literature validated the model and supported the assumptions, suggesting that lethal aberrations lead to cell death 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 supported the idea that the critical DNA lesions leading to cell death (via chromosome aberrations) are a sub-class of DSB showing LET-dependent yields, and that the effects of energy-deposition clustering at the nm scale are modulated by m-scale proximity effects. The model was then applied to predict the fraction of inactivated cells, as well as the yields of lethal aberrations and DNA cluster lesions, as a function of LET; the maximum shown by CL and LA was much higher than that shown by cell inactivation. Acknowledgements: work supported by INFN (project “MiMo-Bragg”).

A BIOPHYSICAL MODEL LINKING RADIATION-INDUCED CHROMOSOME ABERRATIONS AND CELL DEATH

BALLARINI, FRANCESCA;ALTIERI, SAVERIO;BORTOLUSSI, SILVA;GIROLETTI, ELIO;PROTTI, NICOLETTA
2013

Abstract

A mechanism-based model of radiation cell death will be presented, assuming that dicentrics, rings and large deletions (“lethal aberrations” or LA) lead to clonogenic inactivation, and that chromosome aberrations derive from DNA cluster lesions (CL) interacting at the m scale. The CL yield and the threshold distance governing chromosome free-end rejoining are the only model parameters. The model, implemented as a MC code called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations), was applied to AG1522 and V79 cells exposed to photons, alpha particles and heavy ions including Carbon. The agreement with data taken from the literature validated the model and supported the assumptions, suggesting that lethal aberrations lead to cell death 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 supported the idea that the critical DNA lesions leading to cell death (via chromosome aberrations) are a sub-class of DSB showing LET-dependent yields, and that the effects of energy-deposition clustering at the nm scale are modulated by m-scale proximity effects. The model was then applied to predict the fraction of inactivated cells, as well as the yields of lethal aberrations and DNA cluster lesions, as a function of LET; the maximum shown by CL and LA was much higher than that shown by cell inactivation. Acknowledgements: work supported by INFN (project “MiMo-Bragg”).
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11571/721422
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