Carbon-ion irradiation is used to treat deep seated and/or radioresistant tumours because of the ions’ superior ballistic and radiobiological properties compared to low-LET radiation or protons. However, hadrontherapy late effects are undetermined. One such effect may be stress-induced premature senescence (SIPS), a cellular response generally elicited by sublethal insults. By enabling sublethally damaged cells to escape ionising radiation (IR)-induced death, SIPS may lead to genomic instability, hence transformation. Furthermore, in vivo, accumulation of prematurely senescent cells in a normal tissue can affect its performance and accelerate its degeneration. On the other hand, it would be much desirable that lower doses of IR revert the immortalised phenotype to a senescent one or may efficiently impair tumour vasculature. The induction of SIPS and its relationship with telomere length, which drives physiological senescence, were investigated in vitro by exposing model system (HUVEC or human vein endothelial cells) to the GSI carbon ion beam used for therapeutic purposes, at both the LET values incurred by normal (plateau region) and tumour (spread-out Bragg Peak) cells. X-ray irradiation was used as a reference. The aim was two fold: understanding if radiation quality influences SIPS and whether the latter is mechanistically linked with telomere length reduction.

Premature cellular senescence in normal human endothelial cells as a non-lethal effect of low doses of 12C ions: implications for hadrontherapy

MANTI, LORENZO;DURANTE, MARCO;GROSSI, GIANFRANCO;PUGLIESE, MARIAGABRIELLA;SCAMPOLI, PAOLA
2009

Abstract

Carbon-ion irradiation is used to treat deep seated and/or radioresistant tumours because of the ions’ superior ballistic and radiobiological properties compared to low-LET radiation or protons. However, hadrontherapy late effects are undetermined. One such effect may be stress-induced premature senescence (SIPS), a cellular response generally elicited by sublethal insults. By enabling sublethally damaged cells to escape ionising radiation (IR)-induced death, SIPS may lead to genomic instability, hence transformation. Furthermore, in vivo, accumulation of prematurely senescent cells in a normal tissue can affect its performance and accelerate its degeneration. On the other hand, it would be much desirable that lower doses of IR revert the immortalised phenotype to a senescent one or may efficiently impair tumour vasculature. The induction of SIPS and its relationship with telomere length, which drives physiological senescence, were investigated in vitro by exposing model system (HUVEC or human vein endothelial cells) to the GSI carbon ion beam used for therapeutic purposes, at both the LET values incurred by normal (plateau region) and tumour (spread-out Bragg Peak) cells. X-ray irradiation was used as a reference. The aim was two fold: understanding if radiation quality influences SIPS and whether the latter is mechanistically linked with telomere length reduction.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/597336
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