LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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CHAPTER 3 RESULTS exposed to 10 Gy acute dose there was marginal up-regulation of ATM, DNA-PK and Rad52 genes although it was significantly lower than the fractionated group (Fig.3.1.4, A, B, C and D, Lane4). In A549 cells that had been exposed to 2 Gy acute dose there was marginal upregulation of Rad52 and MLH1 genes but these were also significantly lower than the fractionated group(Fig.3.1.4, A, B, C and D, Lane2). 3.1.5 Efficient Repair of DNA It has been established recently that H2AX at the DNA double strand break (DSB) sites are immediately phosphorylated upon irradiation, and the phosphorylated H2AX (γ-H2AX) can be visualized in situ by immunostaining with a γ-H2AX specific antibody [232, 233]. γ-H2AX induction can be measured quantitatively at physiological doses, and the numbers of residual γ- H2AX foci can be used to estimate the kinetics of DSB rejoining. This has become the gold standard for the detection of DSB [233, 234]. Repair kinetics was determined by counting the γ-H2AX foci at 15 min and 4h after irradiation. As expected maximum numbers of foci were seen at 15 min in A549 cells exposed to 10 Gy followed by cells exposed to fractionated irradiation and very few foci were seen in cells exposed to 2 Gy acute dose. By 4h the number of foci in cells exposed to fractionated irradiation had been reduced to almost control but in the cells exposed to 10 Gy the number of foci was still very high, indicating that there was efficient repair of DNA in A549 cells that had been exposed to fractionated irradiation (Fig. 3.1.5). 127
CHAPTER 3 RESULTS 3.1.6 Radiation induced foci of DNA damage response proteins ATM and BRCA1 ATM, an important DNA damage response protein to ionizing radiation and a part of irradiation induced foci (IRIF), is mainly involved in cell cycle arrest and repair. It gets activated after DNA double strand break by phosphorylation at ser 1981 and activates many key cellular proteins that include H2AX, BRCA1, Chk1/2 and p53. Phospho ATM foci and intensity were looked at 4 hours after irradiation. All the cells either exposed to 10 Gy (23±3 foci per cell) or fractionated irradiation (25±2.8 foci per cell) showed ATM foci but only 10% of cells exposed to 2 Gy showed ATM foci and the number of foci per cell was 2±0.08 (Fig. 3.1.6A). The intensity of phosphorylation of ATM was quantified by ImageJ software, was significantly higher in the fractionated group as compared to any of the treatment groups (control, 2Gy or 10Gy ) BRCA1, which is phosphorylated by ATM, is a part of IRIF and shares many downstream substrates of ATM. 4 hours after irradiation, A549 cells that had been exposed to 2 Gy acute dose did not show any BRCA1 foci where as 55 % of cells that had been exposed to fractionated irradiation showed BRCA1 foci and the number of foci per cells was 24±4. 22% of cells that had been exposed to 10 Gy acute showed BRCA1 foci and the number of foci per cell was 15±2.1 (Fig. 3.1.6B). The intensity of phosphorylation of BRCA1 as determined by ImageJ software was significantly higher in the fractionated group as compared to any of the treatment groups (control, 2Gy or 10Gy). 128
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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
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SYNOPSIS Ratio of Rad52 to Actin Ra
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Relative Phosphorylation 45 40 35 3
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SYNOPSIS Fig. 3.3A Clonogenic Cell
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SYNOPSIS (A) Av No. of phospho BRCA
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SYNOPSIS Percentage Survival 120 10
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SYNOPSIS Fig.3.4B. Existance of cro
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SYNOPSIS Fig. 3.4EDNA damage in EL-
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SYNOPSIS subsequent cytotoxicity ca
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SYNOPSIS [4] Hall, E. J. Radiobiolo
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CHAPTER 1 INTRODUCTION INTRODUCTION
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CHAPTER 1 INTRODUCTION 15.8% 9.56%
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CHAPTER 1 INTRODUCTION far apart an
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CHAPTER 1 INTRODUCTION and are more
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CHAPTER 1 INTRODUCTION 1.3 DNA dama
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CHAPTER 1 INTRODUCTION associates w
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CHAPTER 1 INTRODUCTION are unable t
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CHAPTER 1 INTRODUCTION Perhaps one
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CHAPTER 1 INTRODUCTION occurs at DS
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CHAPTER 1 INTRODUCTION related prot
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CHAPTER 1 INTRODUCTION damage must
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CHAPTER 1 INTRODUCTION At the prese
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CHAPTER 1 INTRODUCTION predominant
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CHAPTER 1 INTRODUCTION provide a me
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CHAPTER 1 INTRODUCTION hypersensiti
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CHAPTER 1 INTRODUCTION cycle-specif
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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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Page 88 and 89: CHAPTER 2 MATERIALS AND METHODS MAT
Page 90 and 91: CHAPTER 2 MATERIALS AND METHODS 2.2
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Page 96 and 97: CHAPTER 2 MATERIALS AND METHODS PBS
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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
Page 120 and 121: CHAPTER 3 RESULTS 134 AL045793 METT
Page 122 and 123: CHAPTER 3 RESULTS 58 AF237813 ABAT
Page 124 and 125: CHAPTER 3 RESULTS 127 AI809749 ORMD
Page 126 and 127: CHAPTER 3 RESULTS 31 BE615699 UNC84
Page 128 and 129: CHAPTER 3 RESULTS 47 AF026303 SULT1
Page 130 and 131: CHAPTER 3 RESULTS 117 BF062193 CYor
Page 132 and 133: CHAPTER 3 RESULTS 187 AL036662 ---
Page 134 and 135: CHAPTER 3 RESULTS 52 AV686514 EMP2
Page 138 and 139: CHAPTER 3 RESULTS Fig.3.1.4 Gene ex
Page 140 and 141: CHAPTER 3 RESULTS Fig. 3.1.6 Radiat
Page 142 and 143: CHAPTER 3 RESULTS Fig. 3.1.7 Transl
Page 144 and 145: CHAPTER 3 RESULTS 3.1.9 Stabilizati
Page 146 and 147: CHAPTER 3 RESULTS 23±1.5% (Fig. 3.
Page 148 and 149: CHAPTER 3 RESULTS whereas only the
Page 154 and 155: CHAPTER 3 RESULTS with equal doses
Page 156 and 157: CHAPTER 3 RESULTS Fig.3.3.1.2 Forma
Page 158 and 159: CHAPTER 3 RESULTS Fig.3.3.1.3 Phosp
Page 160 and 161: CHAPTER 3 RESULTS (7.5±0.64) (Fig.
Page 164 and 165: CHAPTER 3 RESULTS Fig.3.3.1.7b Phos
Page 166 and 167: CHAPTER 3 RESULTS 3.3.2 Oxygen beam
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Page 170 and 171: CHAPTER 3 RESULTS 3.3.2.3 Radiation
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Page 180 and 181: CHAPTER 3 RESULTS Fig.3.4.2. Exista
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Page 184 and 185: 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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12 S. Ghosh et al. / Mutation Resea
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Cancer Invest Downloaded from infor
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1568 I. J. Radiation Oncology d Bio
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