LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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CHAPTER 1 INTRODUCTION damage must be an important experimental consideration when examining the potential role of ATM in a given response. Another important experimental consideration is the dose of a given DNA-damaging agent used, as alternative or redundant non-ATMdependent pathways may be engaged at high levels of damage or cellular stress [84, 89]. 1.3.2 Cell Cycle Regulation Once the alarm sensors have set off the alarm, the cell reacts to the damage by stopping cell cycle progression. This allows the cell to assess the damage and then accordingly either repair it or undergo apoptosis. The cell cycle is predominantly blocked at either G 1 -S transition (G 1 -S block) or at the G 2 -M transition (G 2 -M block). Under normal conditions such transitions are orchestrated by specific cyclins and cyclin dependent kinases. However, following damage to the DNA, the blocking of the cell cycle is achieved primarily by p53 and p21 proteins (Fig. 1.3A). p53 Multicellular organisms elicit a complex response to IR, which is hard to separate from the fact that they have evolved to have p53 in checkpoint pathways. The checkpoint thus is not equated with ‘arrest for repair’ that was derived from the extensive studies in yeast. Instead, an additional cell fate of apoptosis is included in the possible outcomes of cell fate in higher eukaryotic systems in response to a variety of stress conditions. p53 plays an important role in the response of IR. It is stabilized in vitro and in vivo after IR. The level of p53 protein accumulation in response to IR primarily results from the intensity of DNA damage. Posttranslational modifications of p53 and its interacting proteins determine its stability and transactivation activity. This stabilization and activation is important for its roles in inducing growth arrest when reversible, which is coupled with 49
CHAPTER 1 INTRODUCTION DNA damage repair to protect cells from the IR damage. Apoptosis occurs in response to a high dose of IR when the damage is irreparable, in order to eliminate the damaged cells. The mechanism by which p53 mediates cell cycle arrest and apoptosis is largely mediated through its target genes, although some transcriptional-independent phenomena have been reported in other systems [111]. The dosage of IR predominantly contributes to the outcomes of cell fate, either survival or death. The role of p53 in DSB repair may involve p53 directly. The role(s) of p53 in the S phase arrest/delay are elusive. Fig. 1.3A: Regulation of Cell Cycle by p53 and p21. Following DNA damage, blocking of the cell cycle is orchestrated by p53 along with p21. 50
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RADIATION INDUCED SIGNALING IN MAMM
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DECLARATION I, hereby declare that
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CONTENTS Page No. SYNOPSIS………
Page 8 and 9: 2.11 Measurement of NO production
Page 10 and 11: PREAMBLE SYNOPSIS Ionising radiatio
Page 12 and 13: SYNOPSIS Aims and Objectives: To St
Page 14 and 15: SYNOPSIS 2.6 Immunofluorescence sta
Page 16 and 17: SYNOPSIS ATM gene expression, which
Page 18 and 19: SYNOPSIS Percentage Survival 100 80
Page 20 and 21: SYNOPSIS Ratio of Rad52 to Actin Ra
Page 22 and 23: Relative Phosphorylation 45 40 35 3
Page 24 and 25: SYNOPSIS Fig. 3.3A Clonogenic Cell
Page 26 and 27: SYNOPSIS (A) Av No. of phospho BRCA
Page 28 and 29: SYNOPSIS Percentage Survival 120 10
Page 30 and 31: SYNOPSIS Fig.3.4B. Existance of cro
Page 32 and 33: SYNOPSIS Fig. 3.4EDNA damage in EL-
Page 34 and 35: SYNOPSIS subsequent cytotoxicity ca
Page 36 and 37: SYNOPSIS [4] Hall, E. J. Radiobiolo
Page 38 and 39: CHAPTER 1 INTRODUCTION INTRODUCTION
Page 40 and 41: CHAPTER 1 INTRODUCTION 15.8% 9.56%
Page 42 and 43: CHAPTER 1 INTRODUCTION far apart an
Page 44 and 45: CHAPTER 1 INTRODUCTION and are more
Page 46 and 47: CHAPTER 1 INTRODUCTION 1.3 DNA dama
Page 48 and 49: CHAPTER 1 INTRODUCTION associates w
Page 50 and 51: CHAPTER 1 INTRODUCTION are unable t
Page 52 and 53: CHAPTER 1 INTRODUCTION Perhaps one
Page 54 and 55: CHAPTER 1 INTRODUCTION occurs at DS
Page 56 and 57: CHAPTER 1 INTRODUCTION related prot
Page 60 and 61: CHAPTER 1 INTRODUCTION At the prese
Page 62 and 63: CHAPTER 1 INTRODUCTION predominant
Page 64 and 65: CHAPTER 1 INTRODUCTION provide a me
Page 66 and 67: CHAPTER 1 INTRODUCTION hypersensiti
Page 68 and 69: CHAPTER 1 INTRODUCTION cycle-specif
Page 70 and 71: CHAPTER 1 INTRODUCTION 1.4 Overview
Page 72 and 73: CHAPTER 1 INTRODUCTION 1.4.1 Radiat
Page 74 and 75: CHAPTER 1 INTRODUCTION interaction
Page 76 and 77: CHAPTER 1 INTRODUCTION p90S6 kinase
Page 78 and 79: CHAPTER 1 INTRODUCTION CD4 (formerl
Page 80 and 81: CHAPTER 1 INTRODUCTION unrepaired d
Page 82 and 83: CHAPTER 1 INTRODUCTION well to the
Page 84 and 85: CHAPTER 1 INTRODUCTION 1.6 Radiatio
Page 86 and 87: CHAPTER 1 INTRODUCTION becomes pote
Page 88 and 89: CHAPTER 2 MATERIALS AND METHODS MAT
Page 90 and 91: CHAPTER 2 MATERIALS AND METHODS 2.2
Page 92 and 93: CHAPTER 2 MATERIALS AND METHODS res
Page 94 and 95: CHAPTER 2 MATERIALS AND METHODS Arr
Page 96 and 97: CHAPTER 2 MATERIALS AND METHODS PBS
Page 98 and 99: CHAPTER 2 MATERIALS AND METHODS the
Page 100 and 101: CHAPTER 2 MATERIALS AND METHODS 2.1
Page 102 and 103: CHAPTER 3 RESULTS RESULTS 93
Page 104 and 105: CHAPTER 3 RESULTS fractionated regi
Page 106 and 107: CHAPTER 3 RESULTS On comparison of
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CHAPTER 3 RESULTS Table 3.1.2A List
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CHAPTER 3 RESULTS 80 NM_002185 IL7R
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CHAPTER 3 RESULTS SAA2 149 AU134977
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CHAPTER 3 RESULTS 221 LOC643167 RNA
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CHAPTER 3 RESULTS 299 BF244402 FBXO
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CHAPTER 3 RESULTS CDK4) 57 AU152107
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CHAPTER 3 RESULTS 134 AL045793 METT
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CHAPTER 3 RESULTS 58 AF237813 ABAT
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CHAPTER 3 RESULTS 127 AI809749 ORMD
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CHAPTER 3 RESULTS 31 BE615699 UNC84
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CHAPTER 3 RESULTS 47 AF026303 SULT1
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CHAPTER 3 RESULTS 117 BF062193 CYor
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CHAPTER 3 RESULTS 187 AL036662 ---
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CHAPTER 3 RESULTS 52 AV686514 EMP2
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CHAPTER 3 RESULTS exposed to 10 Gy
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CHAPTER 3 RESULTS Fig.3.1.4 Gene ex
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CHAPTER 3 RESULTS Fig. 3.1.6 Radiat
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CHAPTER 3 RESULTS Fig. 3.1.7 Transl
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CHAPTER 3 RESULTS 3.1.9 Stabilizati
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CHAPTER 3 RESULTS 23±1.5% (Fig. 3.
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CHAPTER 3 RESULTS whereas only the
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CHAPTER 3 RESULTS with equal doses
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CHAPTER 3 RESULTS Fig.3.3.1.2 Forma
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CHAPTER 3 RESULTS Fig.3.3.1.3 Phosp
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CHAPTER 3 RESULTS (7.5±0.64) (Fig.
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CHAPTER 3 RESULTS Fig.3.3.1.7b Phos
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CHAPTER 3 RESULTS 3.3.2 Oxygen beam
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CHAPTER 3 RESULTS in all the cells.
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CHAPTER 3 RESULTS 3.3.2.3 Radiation
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CHAPTER 3 RESULTS Fig.3.3.2.7 Apopt
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CHAPTER 3 RESULTS PMA stimulated U9
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CHAPTER 3 RESULTS Fig.3.4.2. Exista
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CHAPTER 3 RESULTS up-regulation of
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CHAPTER 3 RESULTS Fig.3.4.3.2 NO pr
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CHAPTER 3 RESULTS 3.4.3.4 Apoptotic
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CHAPTER 3 RESULTS 3.4.4 Bystander e
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CHAPTER 3 RESULTS Fig.3.4.4b DNA da
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CHAPTER 3 RESULTS Fig.3.4.5a Gene e
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CHAPTER 4 DISCUSSION DISCUSSION 185
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CHAPTER 4 DISCUSSION directly expos
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CHAPTER 4 DISCUSSION dose is delive
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CHAPTER 4 DISCUSSION A clear cause
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CHAPTER 4 DISCUSSION 4.2 Proton bea
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CHAPTER 4 DISCUSSION Although the e
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CHAPTER 4 DISCUSSION Similar number
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CHAPTER 4 DISCUSSION the mechanism
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CHAPTER 4 DISCUSSION Thus unlike th
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CHAPTER 4 DISCUSSION different from
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CHAPTER 4 DISCUSSION upregulates ma
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CHAPTER 4 DISCUSSION Numerous studi
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CHAPTER 4 DISCUSSION inhibition of
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CHAPTER 4 DISCUSSION The survival o
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CHAPTER 5 REFERENCES [1] Khan, F. T
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CHAPTER 5 REFERENCES [19] Woo, R. A
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CHAPTER 5 REFERENCES [35] Nghiem, P
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CHAPTER 5 REFERENCES [52] McKay, B.
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CHAPTER 5 REFERENCES [69] Cary, R.
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CHAPTER 5 REFERENCES [84] Uziel, T.
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CHAPTER 5 REFERENCES [98] Liu, Y.;
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CHAPTER 5 REFERENCES [111] Fei, P.;
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CHAPTER 5 REFERENCES [127] Frank, K
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CHAPTER 5 REFERENCES [141] Pierce,
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CHAPTER 5 REFERENCES [156] Roots, R
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CHAPTER 5 REFERENCES [171] Xia, Z.;
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CHAPTER 5 REFERENCES (MAP) kinase c
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CHAPTER 5 REFERENCES phosphorylatio
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CHAPTER 5 REFERENCES [211] Anderson
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CHAPTER 5 REFERENCES [229] Konca, K
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CHAPTER 5 REFERENCES [245] Kastan,
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CHAPTER 5 REFERENCES [261] Miralbel
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CHAPTER 5 REFERENCES [278] Weizman,
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CHAPTER 5 REFERENCES [294] Zhou, H.
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PUBLICATIONS AND PRESENTATIONS Publ
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Mutation Research 729 (2012) 61-72
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S. Ghosh, M. Krishna / Mutation Res
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