The Neoplastic Transformation of SCID Cells by Radiation
Severe combined immunodeficiency (SCID) cells are hypersensitive to killing by ionizing radiation because of deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. The effect of this condition on the neoplastic transformation of...
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Veröffentlicht in: | Radiation research 1999-08, Vol.152 (2), p.180-189 |
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description | Severe combined immunodeficiency (SCID) cells are hypersensitive to killing by ionizing radiation because of deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. The effect of this condition on the neoplastic transformation of SCID fibroblasts, designated SCID 3T1, has been investigated. The spontaneous transformation rate was $\sim 2\times 10^{-5}$ at early passages and increased up to $\sim 7\times 10^{-3}$ at later passages. The radiation survival curves of transformed cells had thresholds and therefore appeared to be qualitatively similar to the survival curves of ${\rm C}3{\rm H}\ 10{\rm T}{\textstyle\frac{1}{2}}$ mouse fibroblast cells, but the initial slopes were steeper. In contrast, per unit dose, SCID cells were more sensitive to transformation than 10T 1/2 cells. Eight transformed clones were tested for tumorigenicity, and all produced fibrosarcomas in athymic nude mice. Properties associated with the tumor suppressor Trp53 (formerly known as p53) were examined in three of the clones. In these clones, although Trp53 protein was overexpressed, a lower expression of Cdkn1a (formerly known as p21, Cip1) protein was observed compared to parental cells. The expression of Trp53 and Cdkn1a and the G1-phase arrest (one set of data on G1-phase delay is included as an example) was not induced by ionizing radiation in these transformed clones; each clone carried a point mutation in Trp53. This suggests that the deficiency in the repair of DNA double-strand breaks increased the tumorigenicity and the genomic instability of transformed SCID cells. |
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L. ; Lang, Sakari ; Chawapun, Nisa ; Elkind, M. M.</creator><creatorcontrib>Lun, Mingyue ; Wells, R. L. ; Lang, Sakari ; Chawapun, Nisa ; Elkind, M. M.</creatorcontrib><description>Severe combined immunodeficiency (SCID) cells are hypersensitive to killing by ionizing radiation because of deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. The effect of this condition on the neoplastic transformation of SCID fibroblasts, designated SCID 3T1, has been investigated. The spontaneous transformation rate was $\sim 2\times 10^{-5}$ at early passages and increased up to $\sim 7\times 10^{-3}$ at later passages. The radiation survival curves of transformed cells had thresholds and therefore appeared to be qualitatively similar to the survival curves of ${\rm C}3{\rm H}\ 10{\rm T}{\textstyle\frac{1}{2}}$ mouse fibroblast cells, but the initial slopes were steeper. In contrast, per unit dose, SCID cells were more sensitive to transformation than 10T 1/2 cells. Eight transformed clones were tested for tumorigenicity, and all produced fibrosarcomas in athymic nude mice. Properties associated with the tumor suppressor Trp53 (formerly known as p53) were examined in three of the clones. In these clones, although Trp53 protein was overexpressed, a lower expression of Cdkn1a (formerly known as p21, Cip1) protein was observed compared to parental cells. The expression of Trp53 and Cdkn1a and the G1-phase arrest (one set of data on G1-phase delay is included as an example) was not induced by ionizing radiation in these transformed clones; each clone carried a point mutation in Trp53. This suggests that the deficiency in the repair of DNA double-strand breaks increased the tumorigenicity and the genomic instability of transformed SCID cells.</description><identifier>ISSN: 0033-7587</identifier><identifier>EISSN: 1938-5404</identifier><identifier>DOI: 10.2307/3580092</identifier><identifier>PMID: 10409328</identifier><identifier>CODEN: RAREAE</identifier><language>eng</language><publisher>Oak Brook, Il: Radiation Research Society</publisher><subject>Animals ; Biological and medical sciences ; Carcinogenesis, carcinogens and anticarcinogens ; Cell cycle ; Cell growth ; Cell lines ; Cell Transformation, Neoplastic - radiation effects ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins - analysis ; DNA ; DNA Repair ; Exons ; G1 Phase ; Genetic mutation ; Male ; Medical sciences ; Mice ; Mice, Nude ; Mice, SCID ; Neoplasms, Radiation-Induced - etiology ; Neoplastic cell transformation ; Physical agents ; Radiotherapy ; Severe combined immunodeficiency ; Severe Combined Immunodeficiency - genetics ; Severe Combined Immunodeficiency - metabolism ; Severe Combined Immunodeficiency - pathology ; Transformed cell line ; Tumor Suppressor Protein p53 - analysis ; Tumors</subject><ispartof>Radiation research, 1999-08, Vol.152 (2), p.180-189</ispartof><rights>Copyright 1999 The Radiation Research Society</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c335t-80731bc6f8aebc13ca71e94d4e411a9af7f22e724ad0b3190e5ae66ca45a3a823</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3580092$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3580092$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1928388$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10409328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lun, Mingyue</creatorcontrib><creatorcontrib>Wells, R. L.</creatorcontrib><creatorcontrib>Lang, Sakari</creatorcontrib><creatorcontrib>Chawapun, Nisa</creatorcontrib><creatorcontrib>Elkind, M. M.</creatorcontrib><title>The Neoplastic Transformation of SCID Cells by Radiation</title><title>Radiation research</title><addtitle>Radiat Res</addtitle><description>Severe combined immunodeficiency (SCID) cells are hypersensitive to killing by ionizing radiation because of deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. The effect of this condition on the neoplastic transformation of SCID fibroblasts, designated SCID 3T1, has been investigated. The spontaneous transformation rate was $\sim 2\times 10^{-5}$ at early passages and increased up to $\sim 7\times 10^{-3}$ at later passages. The radiation survival curves of transformed cells had thresholds and therefore appeared to be qualitatively similar to the survival curves of ${\rm C}3{\rm H}\ 10{\rm T}{\textstyle\frac{1}{2}}$ mouse fibroblast cells, but the initial slopes were steeper. In contrast, per unit dose, SCID cells were more sensitive to transformation than 10T 1/2 cells. Eight transformed clones were tested for tumorigenicity, and all produced fibrosarcomas in athymic nude mice. Properties associated with the tumor suppressor Trp53 (formerly known as p53) were examined in three of the clones. In these clones, although Trp53 protein was overexpressed, a lower expression of Cdkn1a (formerly known as p21, Cip1) protein was observed compared to parental cells. The expression of Trp53 and Cdkn1a and the G1-phase arrest (one set of data on G1-phase delay is included as an example) was not induced by ionizing radiation in these transformed clones; each clone carried a point mutation in Trp53. This suggests that the deficiency in the repair of DNA double-strand breaks increased the tumorigenicity and the genomic instability of transformed SCID cells.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell lines</subject><subject>Cell Transformation, Neoplastic - radiation effects</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - analysis</subject><subject>DNA</subject><subject>DNA Repair</subject><subject>Exons</subject><subject>G1 Phase</subject><subject>Genetic mutation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mice, SCID</subject><subject>Neoplasms, Radiation-Induced - etiology</subject><subject>Neoplastic cell transformation</subject><subject>Physical agents</subject><subject>Radiotherapy</subject><subject>Severe combined immunodeficiency</subject><subject>Severe Combined Immunodeficiency - genetics</subject><subject>Severe Combined Immunodeficiency - metabolism</subject><subject>Severe Combined Immunodeficiency - pathology</subject><subject>Transformed cell line</subject><subject>Tumor Suppressor Protein p53 - analysis</subject><subject>Tumors</subject><issn>0033-7587</issn><issn>1938-5404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1z89LwzAUwPEgiptT_A8kB8FT9eVHm-QonT8GQ0HnubymCXa0a0nqYf-91Q3cxVN45MN7fAm5ZHDLBag7kWoAw4_IlBmhk1SCPCZTACESlWo1IWcxrmGcWWZOyYSBBCO4nhK9-nT0xXV9g3GoLV0F3ETfhRaHutvQztP3fDGnuWuaSMstfcOq_v06Jycem-gu9u-MfDw-rPLnZPn6tMjvl4kVIh0SDUqw0mZeoystExYVc0ZW0knG0KBXnnOnuMQKSsEMuBRdllmUKQrUXMzIzW6vDV2MwfmiD3WLYVswKH7ai337KK92sv8qW1cduF3sCK73AKPFxo-pto5_zoxGH7B1HLrw77lvgI9p8g</recordid><startdate>19990801</startdate><enddate>19990801</enddate><creator>Lun, Mingyue</creator><creator>Wells, R. L.</creator><creator>Lang, Sakari</creator><creator>Chawapun, Nisa</creator><creator>Elkind, M. M.</creator><general>Radiation Research Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>19990801</creationdate><title>The Neoplastic Transformation of SCID Cells by Radiation</title><author>Lun, Mingyue ; Wells, R. L. ; Lang, Sakari ; Chawapun, Nisa ; Elkind, M. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-80731bc6f8aebc13ca71e94d4e411a9af7f22e724ad0b3190e5ae66ca45a3a823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell lines</topic><topic>Cell Transformation, Neoplastic - radiation effects</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclins - analysis</topic><topic>DNA</topic><topic>DNA Repair</topic><topic>Exons</topic><topic>G1 Phase</topic><topic>Genetic mutation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mice, SCID</topic><topic>Neoplasms, Radiation-Induced - etiology</topic><topic>Neoplastic cell transformation</topic><topic>Physical agents</topic><topic>Radiotherapy</topic><topic>Severe combined immunodeficiency</topic><topic>Severe Combined Immunodeficiency - genetics</topic><topic>Severe Combined Immunodeficiency - metabolism</topic><topic>Severe Combined Immunodeficiency - pathology</topic><topic>Transformed cell line</topic><topic>Tumor Suppressor Protein p53 - analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lun, Mingyue</creatorcontrib><creatorcontrib>Wells, R. L.</creatorcontrib><creatorcontrib>Lang, Sakari</creatorcontrib><creatorcontrib>Chawapun, Nisa</creatorcontrib><creatorcontrib>Elkind, M. M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Radiation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lun, Mingyue</au><au>Wells, R. L.</au><au>Lang, Sakari</au><au>Chawapun, Nisa</au><au>Elkind, M. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Neoplastic Transformation of SCID Cells by Radiation</atitle><jtitle>Radiation research</jtitle><addtitle>Radiat Res</addtitle><date>1999-08-01</date><risdate>1999</risdate><volume>152</volume><issue>2</issue><spage>180</spage><epage>189</epage><pages>180-189</pages><issn>0033-7587</issn><eissn>1938-5404</eissn><coden>RAREAE</coden><abstract>Severe combined immunodeficiency (SCID) cells are hypersensitive to killing by ionizing radiation because of deregulation of DNA-dependent protein kinase (DNA-PK) and a concomitant deficiency in the repair of DNA double-strand breaks. The effect of this condition on the neoplastic transformation of SCID fibroblasts, designated SCID 3T1, has been investigated. The spontaneous transformation rate was $\sim 2\times 10^{-5}$ at early passages and increased up to $\sim 7\times 10^{-3}$ at later passages. The radiation survival curves of transformed cells had thresholds and therefore appeared to be qualitatively similar to the survival curves of ${\rm C}3{\rm H}\ 10{\rm T}{\textstyle\frac{1}{2}}$ mouse fibroblast cells, but the initial slopes were steeper. In contrast, per unit dose, SCID cells were more sensitive to transformation than 10T 1/2 cells. Eight transformed clones were tested for tumorigenicity, and all produced fibrosarcomas in athymic nude mice. Properties associated with the tumor suppressor Trp53 (formerly known as p53) were examined in three of the clones. In these clones, although Trp53 protein was overexpressed, a lower expression of Cdkn1a (formerly known as p21, Cip1) protein was observed compared to parental cells. The expression of Trp53 and Cdkn1a and the G1-phase arrest (one set of data on G1-phase delay is included as an example) was not induced by ionizing radiation in these transformed clones; each clone carried a point mutation in Trp53. This suggests that the deficiency in the repair of DNA double-strand breaks increased the tumorigenicity and the genomic instability of transformed SCID cells.</abstract><cop>Oak Brook, Il</cop><pub>Radiation Research Society</pub><pmid>10409328</pmid><doi>10.2307/3580092</doi><tpages>10</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Carcinogenesis, carcinogens and anticarcinogens Cell cycle Cell growth Cell lines Cell Transformation, Neoplastic - radiation effects Cyclin-Dependent Kinase Inhibitor p21 Cyclins - analysis DNA DNA Repair Exons G1 Phase Genetic mutation Male Medical sciences Mice Mice, Nude Mice, SCID Neoplasms, Radiation-Induced - etiology Neoplastic cell transformation Physical agents Radiotherapy Severe combined immunodeficiency Severe Combined Immunodeficiency - genetics Severe Combined Immunodeficiency - metabolism Severe Combined Immunodeficiency - pathology Transformed cell line Tumor Suppressor Protein p53 - analysis Tumors |
title | The Neoplastic Transformation of SCID Cells by Radiation |
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