Functional genomic investigation of the molecular biological impact of electron beam radiation in lymphoma cells
Abstract Purpose The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. Methods Mouse model bearing Dalton’s lymphoma ascites (DLA) cells were exposed to 8 MeV pulsed electron b...
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| Veröffentlicht in: | Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2016-05, Vol.16 (5), p.253-263.e6 |
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| creator | Gopal, Ramani Rani, Usha Murugesan, Ram Kumar, Kirushna Sanjeev, Ganesh Ganesan, Kumaresan |
| description | Abstract Purpose The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. Methods Mouse model bearing Dalton’s lymphoma ascites (DLA) cells were exposed to 8 MeV pulsed electron beam, at a dose rate of 2 Gy min-1 using microtron, a linear accelerator (linac). Radiation induced changes were assessed by histopathology, FACS, signaling pathway focused reporter assays and gene expression by microarray analysis. Results EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo . Microarray data revealed that EBR induced tumor regression, apoptosis and cell cycle arrest mediated by p53, PPAR and SMAD2/3/4 signaling pathways. Activation of IRF & NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. Conclusion For the first time, 8 MeV pulse EBR induced genomic changes and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR. |
| doi_str_mv | 10.1016/j.clml.2016.02.033 |
| format | Article |
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This study describes the molecular biological and genomic impact of EBR on tumor cells. Methods Mouse model bearing Dalton’s lymphoma ascites (DLA) cells were exposed to 8 MeV pulsed electron beam, at a dose rate of 2 Gy min-1 using microtron, a linear accelerator (linac). Radiation induced changes were assessed by histopathology, FACS, signaling pathway focused reporter assays and gene expression by microarray analysis. Results EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo . Microarray data revealed that EBR induced tumor regression, apoptosis and cell cycle arrest mediated by p53, PPAR and SMAD2/3/4 signaling pathways. Activation of IRF & NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. Conclusion For the first time, 8 MeV pulse EBR induced genomic changes and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR.</description><identifier>ISSN: 2152-2650</identifier><identifier>EISSN: 2152-2669</identifier><identifier>DOI: 10.1016/j.clml.2016.02.033</identifier><identifier>PMID: 27061493</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Cycle Checkpoints - radiation effects ; Cell Line, Tumor ; Chemo-genomics ; Chemosensitivity ; Cluster Analysis ; Computational Biology - methods ; Disease Models, Animal ; Drug Resistance, Neoplasm - genetics ; Electrons - therapeutic use ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic - drug effects ; Genomics - methods ; Hematology, Oncology and Palliative Medicine ; Humans ; Lymphoma - genetics ; Lymphoma - pathology ; Lymphoma - radiotherapy ; Male ; Mice ; Microtron ; Radiation, Ionizing ; Radiotherapy ; Signal Transduction - radiation effects ; Transcriptome ; Tumor Burden - radiation effects ; Xenograft Model Antitumor Assays</subject><ispartof>Clinical lymphoma, myeloma and leukemia, 2016-05, Vol.16 (5), p.253-263.e6</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c362t-ba252fa855636225b0ac91a339f2c88184f2a53d1bf41929aa5cb9b30f00a8253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clml.2016.02.033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27061493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gopal, Ramani</creatorcontrib><creatorcontrib>Rani, Usha</creatorcontrib><creatorcontrib>Murugesan, Ram</creatorcontrib><creatorcontrib>Kumar, Kirushna</creatorcontrib><creatorcontrib>Sanjeev, Ganesh</creatorcontrib><creatorcontrib>Ganesan, Kumaresan</creatorcontrib><title>Functional genomic investigation of the molecular biological impact of electron beam radiation in lymphoma cells</title><title>Clinical lymphoma, myeloma and leukemia</title><addtitle>Clin Lymphoma Myeloma Leuk</addtitle><description>Abstract Purpose The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. Methods Mouse model bearing Dalton’s lymphoma ascites (DLA) cells were exposed to 8 MeV pulsed electron beam, at a dose rate of 2 Gy min-1 using microtron, a linear accelerator (linac). Radiation induced changes were assessed by histopathology, FACS, signaling pathway focused reporter assays and gene expression by microarray analysis. Results EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo . Microarray data revealed that EBR induced tumor regression, apoptosis and cell cycle arrest mediated by p53, PPAR and SMAD2/3/4 signaling pathways. Activation of IRF & NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. Conclusion For the first time, 8 MeV pulse EBR induced genomic changes and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR.</description><subject>Animals</subject><subject>Cell Cycle Checkpoints - radiation effects</subject><subject>Cell Line, Tumor</subject><subject>Chemo-genomics</subject><subject>Chemosensitivity</subject><subject>Cluster Analysis</subject><subject>Computational Biology - methods</subject><subject>Disease Models, Animal</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Electrons - therapeutic use</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genomics - methods</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Lymphoma - genetics</subject><subject>Lymphoma - pathology</subject><subject>Lymphoma - radiotherapy</subject><subject>Male</subject><subject>Mice</subject><subject>Microtron</subject><subject>Radiation, Ionizing</subject><subject>Radiotherapy</subject><subject>Signal Transduction - radiation effects</subject><subject>Transcriptome</subject><subject>Tumor Burden - radiation effects</subject><subject>Xenograft Model Antitumor Assays</subject><issn>2152-2650</issn><issn>2152-2669</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUGPFCEQhYnRuOvqH_BgOHqZtiiG7iYxJmbjqskmHtQzoWl6lhGaFro3mX8vZNY9ePBEAe-9VH1FyGsGDQPWvjs2xgffYKkbwAY4f0IukQncYdvKp4-1gAvyIucjQAfA5HNygR20bC_5JVluttmsLs7a04OdY3CGuvne5tUddH2ncaLrnaUhems2rxMdXPTx4ExxuLBos1aJLb9rKvLB6kCTHt3Z7WbqT2G5i0FTY73PL8mzSftsXz2cV-Tnzacf1192t98-f73-eLszvMV1N2gUOOleiLbcUQygjWSaczmh6XvW7yfUgo9smPZMotRamEEOHCYA3aPgV-TtOXdJ8fdW5lHB5dqBnm3csmJd3-075IBFimepSTHnZCe1JBd0OikGqpJWR1VJq0paAapCupjePORvQ7Djo-Uv2iJ4fxbYMuW9s0ll4-xs7OhSYaXG6P6f_-Efu_FurtR_2ZPNx7ilsrMyh8rFoL7XXddVsxYAJO_5H75apVw</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Gopal, Ramani</creator><creator>Rani, Usha</creator><creator>Murugesan, Ram</creator><creator>Kumar, Kirushna</creator><creator>Sanjeev, Ganesh</creator><creator>Ganesan, Kumaresan</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160501</creationdate><title>Functional genomic investigation of the molecular biological impact of electron beam radiation in lymphoma cells</title><author>Gopal, Ramani ; Rani, Usha ; Murugesan, Ram ; Kumar, Kirushna ; Sanjeev, Ganesh ; Ganesan, Kumaresan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-ba252fa855636225b0ac91a339f2c88184f2a53d1bf41929aa5cb9b30f00a8253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Cell Cycle Checkpoints - radiation effects</topic><topic>Cell Line, Tumor</topic><topic>Chemo-genomics</topic><topic>Chemosensitivity</topic><topic>Cluster Analysis</topic><topic>Computational Biology - methods</topic><topic>Disease Models, Animal</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Electrons - therapeutic use</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Genomics - methods</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Lymphoma - genetics</topic><topic>Lymphoma - pathology</topic><topic>Lymphoma - radiotherapy</topic><topic>Male</topic><topic>Mice</topic><topic>Microtron</topic><topic>Radiation, Ionizing</topic><topic>Radiotherapy</topic><topic>Signal Transduction - radiation effects</topic><topic>Transcriptome</topic><topic>Tumor Burden - radiation effects</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gopal, Ramani</creatorcontrib><creatorcontrib>Rani, Usha</creatorcontrib><creatorcontrib>Murugesan, Ram</creatorcontrib><creatorcontrib>Kumar, Kirushna</creatorcontrib><creatorcontrib>Sanjeev, Ganesh</creatorcontrib><creatorcontrib>Ganesan, Kumaresan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical lymphoma, myeloma and leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gopal, Ramani</au><au>Rani, Usha</au><au>Murugesan, Ram</au><au>Kumar, Kirushna</au><au>Sanjeev, Ganesh</au><au>Ganesan, Kumaresan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional genomic investigation of the molecular biological impact of electron beam radiation in lymphoma cells</atitle><jtitle>Clinical lymphoma, myeloma and leukemia</jtitle><addtitle>Clin Lymphoma Myeloma Leuk</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>16</volume><issue>5</issue><spage>253</spage><epage>263.e6</epage><pages>253-263.e6</pages><issn>2152-2650</issn><eissn>2152-2669</eissn><abstract>Abstract Purpose The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. Methods Mouse model bearing Dalton’s lymphoma ascites (DLA) cells were exposed to 8 MeV pulsed electron beam, at a dose rate of 2 Gy min-1 using microtron, a linear accelerator (linac). Radiation induced changes were assessed by histopathology, FACS, signaling pathway focused reporter assays and gene expression by microarray analysis. Results EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo . Microarray data revealed that EBR induced tumor regression, apoptosis and cell cycle arrest mediated by p53, PPAR and SMAD2/3/4 signaling pathways. Activation of IRF & NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. Conclusion For the first time, 8 MeV pulse EBR induced genomic changes and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27061493</pmid><doi>10.1016/j.clml.2016.02.033</doi></addata></record> |
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| subjects | Animals Cell Cycle Checkpoints - radiation effects Cell Line, Tumor Chemo-genomics Chemosensitivity Cluster Analysis Computational Biology - methods Disease Models, Animal Drug Resistance, Neoplasm - genetics Electrons - therapeutic use Gene Expression Profiling Gene Expression Regulation, Neoplastic - drug effects Genomics - methods Hematology, Oncology and Palliative Medicine Humans Lymphoma - genetics Lymphoma - pathology Lymphoma - radiotherapy Male Mice Microtron Radiation, Ionizing Radiotherapy Signal Transduction - radiation effects Transcriptome Tumor Burden - radiation effects Xenograft Model Antitumor Assays |
| title | Functional genomic investigation of the molecular biological impact of electron beam radiation in lymphoma cells |
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