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• W2079297041 endingPage "2033" @default.
• W2079297041 startingPage "2023" @default.
• W2079297041 abstract "Proton radiation (PR) therapy offers a number of potential advantages over conventional(photon) gamma-radiation (GR) therapy for cancer, due to a more localized delivery ofthe radiation dose. However, the pathophysiological effects following PR-exposure areless well characterized than those of GR-exposure and the molecular changes associatedwith the acute apoptotic effects in mice in vivo following PR have not been elucidated.Previous studies have estimated the RBE of protons for various in vivo and in vitroendpoints at between 1.1 and 1.3. We assumed an RBE of 1.1 for the endpoints to beevaluated in these studies. Based on this assumption, ICR mice were treated with wholebodydoses of GR (1.1 and 7.0 Gy) and PR (1.0 and 6.4 Gy) that were expected torepresent RBE-weighted doses. The bone marrow, thymus, spleen and GI-tract wereisolated and processed for histology and immunohistochemistry. The apoptotic responsesvaried greatly between GR and PR in a tissue- and dose-dependent manner. Surprisingly,cell death in the splenic white pulp was consistently lower in PR-treated animalscompared to animals treated with GR. This was in spite of an increased presence ofdamaged DNA following PR as determined by staining for gamma-H2AX and phospho-ATM. Interestingly, both PR and GR triggered nuclear accumulation of p53 and nosignificant differences were found in the majority of the known pro-apoptotic p53-targetgenes in the spleens of treated mice. However, GR uniquely triggered a pro-apoptoticexpression profile including expression of the pro-apoptotic, p53- and interferonstimulated target gene bcl-g. In contrast to PR, GR may, in a cell type specific manner,trigger a more diverse non-random stress-response that mediates apoptosis partiallyindependent of the extent of DNA damage." @default.
• W2079297041 created "2016-06-24" @default.
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• W2079297041 date "2008-12-01" @default.
• W2079297041 modified "2023-10-01" @default.
• W2079297041 title "Gamma-radiation (GR) triggers a unique gene expression profile associated with cell death compared to proton radiation (PR) in mice in vivo" @default.
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• W2079297041 doi "https://doi.org/10.4161/cbt.7.12.7417" @default.
• W2079297041 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3590842" @default.
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