LIFE01200604005 Shri Somnath Ghosh - Homi Bhabha National ...

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Cancer Invest Downloaded from informahealthcare.com by University of Chicago Library on 06/10/11 For personal use only. Figure 2. Gene expression of ATM, DNA-PK, ATR, Chk1, and Chk2 in A549 cells irradiated with 2 Gy proton beam or 2 Gy γ-radiation at 2, 3, or 4 hr after irradiation. Total RNA from A549 cells was isolated and reverse transcribed. RT-PCR analysis of ATM, DNA-PK, ATR, Chk1, and Chk2 genes was carried out as described in materials and methods. PCR products were resolved on 1.5% agarose gels containing ethidium bromide. β-actin gene expression in each group was used as an internal control. Ratio of intensities of (A and B) ATM, DNA-PK, or ATR and (C and D) Chk1 and Chk2 band to that of respective β-actin band as quantified from gel pictures are shown above each gel picture. Con means unirradiated control. Data represents means ± SE of three independent experiments, significantly different from unirradiated controls. ∗ p < .05, ∗∗ p < .01. response in eukaryotes (24). It was of interest to look for its phosphorylation and its substrates at 4 hr after irradiation. There was significantly higher phosphorylation of ATM at serine 1981, H2AX at γ -position, Chk2 at threonine 68, and p53 at serine 15 in A549 cells which had been exposed to 2 Gy of proton beam, but their phosphorylation was not found to be increased 4 hr after 2 Gy of γ -radiation as compared to the control (Figure 3). Expression of apoptosis-related genes Since there was significantly higher phosphorylation of p53 in A549 cells which had been exposed to 2 Gy proton beam (Figure 3), it was our interest to look for the expression of apoptosis-related gene like Bax and Bcl-2. In our study, there was significant upregulation of proapoptotic gene, Bax, 12 hr after irradiation in A549 cells, which had been exposed to 2 Gy proton beam as compared to the unirradiated control. In γ -irradiated (2 Gy) cells there was no significant upregulation of the Bax gene (p < .05) (Figure 4). On the other hand there was significant downregulation of antiapoptotic gene, Bcl-2, 12 hr after irradiation in A549 cells, which had been exposed to 2 Gy proton beam. However, following γ -irradiation there was no significant downregulation of Bcl-2 gene. (p < .05) (Figure 4). 618 S. <strong>Ghosh</strong> et al.
Cancer Invest Downloaded from informahealthcare.com by University of Chicago Library on 06/10/11 For personal use only. Figure 3. Immunofluorescence staining and Image analysis of γ-H2AX, phospho-ATM, phospho-Chk2, and phospho-p53 4 hr after irradiation in A549 cells irradiated with 2 Gy proton beam or 2 Gy γ-radiation. Cells were fixed in 4% paraformaldehyde, permeabilized in 0.25% Triton X-100, and labeled with specific antibodies as described in “Materials and Methods.” 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). All images were captured using Carl Zeiss confocal microscope with the same exposure time. (A)–(D) shows the comparison of phosphorylation between 2 Gy proton beam and 2 Gy γ-radiation of [(A) H2AX, (B) ATM, (C) Chk2, (D) p53]. (E) Graph represents relative phosphorylation of H2AX, ATM, Chk2, and p53 as determined by ImageJ software. At least 100 cells per experiment were analyzed from three independent experiments. Data represents means ± SE of three independent experiments, significantly different from unirradiated controls. ∗ p < .05, ∗∗ p < .01. Efficient Cell killing by Proton Beam 619
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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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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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Page 262 and 263: PUBLICATIONS AND PRESENTATIONS Publ
Page 264 and 265: Mutation Research 729 (2012) 61-72
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