LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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S. <strong>Ghosh</strong>, M. Krishna / Mutation Research 729 (2012) 61–72 65 Fig. 3. Gene expression of ATM, DNA-PK, Rad52 and MLH1 in A549 cells irradiated with different doses of -radiation. Total RNA from A549 cells was isolated and reverse transcribed 4 h after irradiation. RT-PCR analysis of ATM, DNA-PK, Rad52 and MLH1 genes was carried out as described in Section 2. PCR products were resolved on 1.5% agarose gels containing ethidium bromide. -Actin gene expression in each group was used as an internal control. Ratio of intensities of (A) ATM, (B) DNA-PK, (C) Rad52 and (D) MLH1 band to that of respective -actin band as quantified from gel pictures are shown above each gel picture. 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 -irradiation; Lane 3, 2 Gy of 60 Co -irradiation daily over a period of 5 days; Lane 4, 10 Gy acute (which is the sum total of all the fraction) 60 Co -irradiation. Data represent means ± SE of three independent experiments; significantly different from unirradiated controls: *P < 0.05, **P < 0.01. study human lung adenocarcinoma A549 cells were found to be more radioresistant if 10 Gy dose was delivered as 5 fractions of 2 Gy dose. Although fractionation is supposed to play an important role in inducing an adaptive response and deciding the fate of cells, the mechanism by which it does so can be many and innumerable factors could be responsible. DNA microarray analysis is a powerful tool for obtaining comprehensive information concerning expression of thousands of genes in cancer cells [45] DNA microarray analysis revealed variable expression of many genes. Up-regulated genes in A549 cells exposed to fractionated irradiation were associated with p53 signaling pathway, cytokine-cytokine receptor interaction, hematopoietic cell lineage, toll-like receptor signaling pathway, Jak-STAT signaling pathway, MAPK signaling pathway, cell-cycle check point, B cell receptor signaling pathway, DNA replication, mismatch repair, homologous recombination. Toll-like receptor signaling pathway is responsible for survival and proliferation of the cells [46]. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of several cell types [47]. MAPK signaling pathways are known to be involved in various processes of growth, differentiation and cell death [48]. Most of the pathways which were up-regulated in A549 cells exposed to fractionated irradiation in all comparisons were associated with the survival or repair of the A549 cells. This indicates that fractionated irradiation could induce up-regulation of survival/repair related pathways in cancer cells. To the authors’ knowledge, this is the first report indicating the differential gene expression profiles of A549 cells exposed to fractionated irradiation. Previous reports concerning
66 S. <strong>Ghosh</strong>, M. Krishna / Mutation Research 729 (2012) 61–72 Fig. 4. Repair kinetics as determined by -H2AX foci in different treatment group of A549 cells at 15 min and 4 h after irradiation. Cells were fixed 15 min and 4 h after irradiation in 4% paraformaldehyde, permeabilized in 0.25% Triton X-100 and labeled with specific antibodies as described in Section 2. Each phospho-site antibody was indirectly labeled with Molecular Probe 488 secondary antibody (green) and cells were mounted with ProLong Gold antifede with DAPI (blue). The encircled area roughly represents cell nuclei as seen by DAPI staining. All images were captured using Carl Zeiss confocal microscope with the same exposure time. Representative image of three independent experiments is shown here; at least 100 cells per experiment were analyzed from three independent experiments. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.) radioresistant non-small-cell lung cancer and HeLa cells also indicated that cell cycle signaling pathways, mismatch repair, homologous recombination were up-regulated [49,50]. In the current study, some of these genes were previously known to be associated with responsiveness to radiation, such as p21 and GADD45˛, but others were novel. These novel genes can be expected to be involved in radioresistance, but the precise function of each gene remains unclear; so further study is necessary to clarify the nature of associations. Microarray data had shown that p53 signaling pathway was up-regulated in A549 cells that had been exposed to fractionated
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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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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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Page 222 and 223: CHAPTER 5 REFERENCES [1] Khan, F. T
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Page 232 and 233: CHAPTER 5 REFERENCES [84] Uziel, T.
Page 234 and 235: CHAPTER 5 REFERENCES [98] Liu, Y.;
Page 236 and 237: CHAPTER 5 REFERENCES [111] Fei, P.;
Page 238 and 239: CHAPTER 5 REFERENCES [127] Frank, K
Page 240 and 241: CHAPTER 5 REFERENCES [141] Pierce,
Page 242 and 243: CHAPTER 5 REFERENCES [156] Roots, R
Page 244 and 245: CHAPTER 5 REFERENCES [171] Xia, Z.;
Page 246 and 247: CHAPTER 5 REFERENCES (MAP) kinase c
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Page 252 and 253: CHAPTER 5 REFERENCES [229] Konca, K
Page 254 and 255: CHAPTER 5 REFERENCES [245] Kastan,
Page 256 and 257: CHAPTER 5 REFERENCES [261] Miralbel
Page 258 and 259: CHAPTER 5 REFERENCES [278] Weizman,
Page 260 and 261: CHAPTER 5 REFERENCES [294] Zhou, H.
Page 262 and 263: PUBLICATIONS AND PRESENTATIONS Publ
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