LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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CHAPTER 1 INTRODUCTION 1.4 Overview of Radiation induced cell signaling Exposure of cells to ionizing radiation results in complex cellular responses resulting in cell death and altered proliferation states. The underlying cytotoxic, cytoprotective and cellular stress responses to radiation are mediated by existing signaling pathways, activation of which may be amplified by intrinsic cellular radical production systems. These signaling responses include the activation of plasma membrane receptors, the stimulation of cytoplasmic protein kinases, transcriptional activation, and altered cell cycle regulation. There is increasing evidence for the functional links between cellular signal transduction responses and DNA damage recognition and repair, cell survival, or cell death through apoptosis or reproductive mechanisms. Recent radiobiological studies have demonstrated that the exposure of mammalian cells to ionizing radiation over a wide dose range results in activation of existing cellular response pathways. These pathways, dominantly involving protein kinases, mediate the cytoprotective and cytotoxic responses of cell survival and cell death, respectively. Cytoprotective responses involve pathways of the mitogen activated protein kinase (MAPK) and phosphatidyl inositol- 3-phosphate kinase (PI3 kinase) cascades which activate the machinery of biosynthesis and may stimulate cell proliferation if radiation-induced damage is successfully repaired. The most direct consequence of cytotoxic or stress responses is thought to involve Jun N-terminal kinase (JNK, now known as MAPK8) and results in apoptosis and/or other forms of cell death. Although general statements may be premature, current data suggest that cells of the hematopoietic lineage and fibroblasts or other normal cells are substantially more prone to undergo radiation-induced apoptosis than many carcinoma cells. 61
CHAPTER 1 INTRODUCTION The goal of this chapter is to describe the complexity of the responses of cells to exposure to ionizing radiation. Links between the mechanisms of various sensors of radiation effects and the activation of major cellular response pathways will be emphasized where possible (Fig. 1.4). The response networks include cytokines and plasma membrane receptors, effector protein kinases, and phosphatases in the cytoplasm or at the interfaces of plasma membrane and nucleus. The extent of radiation-induced changes in proteins, lipids and nucleic acids, the latter recognized by defined proteins as DNA damage, is likely to determine the relative balance between plasma membrane events, mitochondrial reactions, and nuclear responses EFFECT OF IONIZING RADIATION ON CELLULAR RESPONSE SYSTEM RADIATION SENSOR/ROS, RNS AMPLIFIER SIGNAL TRANSDUCTION CELL CYCLE CONTROL CYTOPROTECTIVE SURVIVAL CYTOTOXICITY DEATH: APOPTOSIS/ REPRODUCTIVE DEATH FIG. 1.4 Effects of ionizing radiation on cellular response systems. Radiation effects are mediated through the interaction of radicals and reactive oxygen and nitrogen species (ROS/RNS), with proteins, lipids and nucleic acids; these radicals may be generated from primary ionization events or through secondary amplification systems. Biological molecules that are modified by radicals and generate or transmit intracellular signals are components of existing cellular signal transduction pathways. Effectors of these systems are linked to cell cycle regulation and DNA repair, which determine the ultimate fate of cells exposed to radiation. 62
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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………
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2.11 Measurement of NO production
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PREAMBLE SYNOPSIS Ionising radiatio
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SYNOPSIS Aims and Objectives: To St
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SYNOPSIS 2.6 Immunofluorescence sta
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SYNOPSIS ATM gene expression, which
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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
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Page 50 and 51: CHAPTER 1 INTRODUCTION are unable t
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Page 54 and 55: CHAPTER 1 INTRODUCTION occurs at DS
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Page 58 and 59: CHAPTER 1 INTRODUCTION damage must
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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
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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
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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
Page 108 and 109: CHAPTER 3 RESULTS Table 3.1.2A List
Page 110 and 111: CHAPTER 3 RESULTS 80 NM_002185 IL7R
Page 112 and 113: CHAPTER 3 RESULTS SAA2 149 AU134977
Page 114 and 115: CHAPTER 3 RESULTS 221 LOC643167 RNA
Page 116 and 117: CHAPTER 3 RESULTS 299 BF244402 FBXO
Page 118 and 119: 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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Cancer Invest Downloaded from infor
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1568 I. J. Radiation Oncology d Bio
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