LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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SYNOPSIS Ratio of Rad52 to Actin Ratio of MLH1 to Actin 140 120 100 80 60 40 20 0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Role of Rad 52 and MLH1 in relative radioresistance Con 2Gy 5X2Gy 10Gy Con 2Gy 5X2Gy 10Gy Rad52 Actin MLH1 Ratio of Rad52 to Actin Ratio of MLH1 to Actin 0.6 0.5 0.4 0.3 0.2 0.1 0.0 1.0 0.8 0.6 0.4 0.2 0.0 Con 2Gy 5X2Gy 10Gy Treatment Con 2Gy 5X2Gy 10Gy Treatment Rad52 MLH1 Rad52 Actin MLH1 Actin A549 cells Actin MCF-7 cells Fig. 3.1E. Gene expression of Rad52 and MLH1 in MCF-7 and A 549 cells. Key; Lane 1, control unirradiated A549 cell line. Lane 2, 2 Gy acute dose ( single dose that was delivered in each fraction ) of 60 Co γ-irradiation Lane 3 2 Gy of 60 Co γ-irradiation daily over a period of 5 days, Lane 4, 10 Gy acute (which is the sum total of all the fraction ) 60 Co γ-irradiation. mRNA stability of DNA-PK Relative expression of DNA-PK 30000 25000 20000 15000 10000 5000 0 2h+Act 2h+Act+In 4h+Act 4h+Act+In 6h+Act 6h+Act+In 8h+Act 8h+Act+In Time (h) 2 2 4 4 6 6 8 8 Actinomycin (5mg/ml) + + + + + + + + p38 MAPK inhibitor (1µM) - + - + - + - + DNA-PK Fig. 3.1F Stabilization of DNA-PK mRNA in A549, which had been exposed to 2 Gy of 60 Co γ-irradiation daily over a period of 5 days and its stabilization is control by p38 MAP Kinase. 11
Role of Rad52 and MLH1 In relative radioresistance of A549 cells SYNOPSIS Control 5X2Gy 5X2Gy + MLH1 5X2Gy + Rad52 Fig. 3.1G Inhibition of Rad52 with its SiRNA reversed the radioresistance of the A549 cells and made it sensitive to fractionated irradiation. Key; Lane 1, control unirradiated A549 cell line. Lane 2, 2 Gy of 60 Co γ-irradiation daily over a period of 5 days Lane 3, A 549 cells transfected with MLH1 SiRNA and exposed to 2 Gy of 60 Co γ-irradiation daily over a period of 5 days, Lane 4, A 549 cells transfected with Rad52 SiRNA and exposed to 2 Gy of 60 Co γ-irradiation daily over a period of 5 days. Fig. 3.2A Clonogenic Cell Survival of A 549 cells irradiated with 2Gy Proton Beam or 2Gy γ-radiation. Data shown from representative experiment of three independent experiments. 12
Page 1: RADIATION INDUCED SIGNALING IN MAMM
Page 4 and 5: DECLARATION I, hereby declare that
Page 6 and 7: 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 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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CHAPTER 1 INTRODUCTION 1.4 Overview
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CHAPTER 1 INTRODUCTION 1.4.1 Radiat
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CHAPTER 1 INTRODUCTION interaction
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CHAPTER 1 INTRODUCTION p90S6 kinase
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CHAPTER 1 INTRODUCTION CD4 (formerl
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CHAPTER 1 INTRODUCTION unrepaired d
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CHAPTER 1 INTRODUCTION well to the
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CHAPTER 1 INTRODUCTION 1.6 Radiatio
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CHAPTER 1 INTRODUCTION becomes pote
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CHAPTER 2 MATERIALS AND METHODS MAT
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CHAPTER 2 MATERIALS AND METHODS 2.2
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CHAPTER 2 MATERIALS AND METHODS res
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CHAPTER 2 MATERIALS AND METHODS Arr
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CHAPTER 2 MATERIALS AND METHODS PBS
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CHAPTER 2 MATERIALS AND METHODS the
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CHAPTER 2 MATERIALS AND METHODS 2.1
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CHAPTER 3 RESULTS RESULTS 93
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CHAPTER 3 RESULTS fractionated regi
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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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Cancer Invest Downloaded from infor
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1568 I. J. Radiation Oncology d Bio
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