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Title: Effects of different ion species and LETs on glioblastoma cell lines
Author: Chew, Ming T.
ISNI:       0000 0004 6494 7922
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2017
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Glioblastoma (GBM) is a known photon radio-resistant tumour and charged ion therapy could be an alternative treatment to improve survival and quality of life. This work aims to determine the effects of ion species, 4He, 12C, 20Ne, 28Si and 56Fe and photon 200 kVp X-rays - 1.7 keV/µm on three different glioblastoma cell lines, T98G, U87 and LN18. Their capacity for potential lethal damage repair (PLDR) was also examined. Mono-energetic beams of 4He, 12C, 20Ne, 28Si and 56Fe were generated by the Heavy Ion Medical Accelerator at Chiba at the National Institute of Radiological Sciences (NIRS) in Chiba, Japan. X-rays experiments were also performed at NIRS. The linear energy transfer (LET) of charged ions used ranges from 2.3 - 200 keV/µm, covering the entrance (plateau) to clinically relevant and high LETs that simulate space radiation. Space radiation biology was an opportunistic study at NIRS. Exposure to space radiation is known to be a high risk to the central nervous system. It is acknowledged that there are benefits and limitations of using GBM cell lines to study space radiation. Using GBM cell line which arises from the brain may aid in the understanding of the effects of space radiation to the brain. Moreover, some strains of GBM cell lines are low dose hypersensitive and very low doses that are used to study space radiation maybe relevant. The limitation is that they are not normal cells such as the lymphocytes or fibroblast; hence, restrictions may have to be applied when interpreting these results. Clonogenic assay was used to determine the efficacy of the radiations. For potential lethal damage repair (PLDR) study, the cells were allowed 24 hours to repair before plating out. Results show that LN18 relative biological effectiveness at 10% survival (RBE10) increases with LET and peaks 85 at keV/µm; however, both T98G and U87 at 200 keV/µm. LN18 α (single hit kill) peaks at 200 keV/µm, whereas, U87 and T98G peak at 100 keV/µm. The statistical significance between the mean of RBE10; and of the mean of α between the three GBM cell lines (p < 0.01) demonstrates that each GBM cell line response uniquely to the similar ion and LET. Linear regression line shows there is a linear relationship between α and RBE as a function of LET for all three cell lines. Additionally, GBM cells have the capability to repair potential lethal damage induced by radiations; and are LET and dose dependent. Keywords: Glioblastoma (GBM), ion therapy, carbon ions, neon ions, helium ions, silicon ions, iron ions, PLDR, PLDR-ratio, LET, RBE10, RBE2 Gy, RSF2 Gy, α parameter, β parameter, α/β ratio, and space radiation.
Supervisor: Not available Sponsor: FP7-215840-2/Marie Curie ; International Open Laboratory (IOL) ; Chiba ; Japan ; NIRS/HIMAC ; Chiba ; Japan
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available