Human In vivo Dose-Response to Controlled, Low-Dose Low Linear Energy Transfer Ionizing Radiation Exposure
Purpose: The effect of low doses of low–linear energy transfer (photon) ionizing radiation (LDIR,
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| Veröffentlicht in: | Clinical cancer research 2006-06, Vol.12 (12), p.3723-3729 |
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| creator | GOLDBERG, Zelanna ROCKE, David M SCHWIETERT, Chad BERGLUND, Susanne R SANTANA, Alison JONES, Angela LEHMANN, Jbrg STERN, Robin RUIXIAO LU HARTMANN SIANTAR, Christine |
| description | Purpose: The effect of low doses of low–linear energy transfer (photon) ionizing radiation (LDIR, |
| doi_str_mv | 10.1158/1078-0432.CCR-05-2625 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17272521</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17272521</sourcerecordid><originalsourceid>FETCH-LOGICAL-c449t-1b46ac6c3d61cb1b8674dd8cecb9c6c8878bbc905365e7c4e42f0e7d0043001a3</originalsourceid><addsrcrecordid>eNpFkG1rFDEQgIMotlZ_gpIvCoJb87rJfizraQ8OhKN-Dtns7F3KXnImu63115vlTgoDMwzPzDAPQu8puaZU6q-UKF0Rwdl1224rIitWM_kCXVIpVcVZLV-W-j9zgd7kfE8IFZSI1-iC1kpp0jSX6P52PtiA1wE_-IeIv8UM1RbyMYYMeIq4jWFKcRyh_4I38bFagKXAGx_AJrwKkHZP-C7ZkAdIeB2D_-vDDm9t7-3kY8CrP8eY5wRv0avBjhnenfMV-vV9ddfeVpufP9btzaZyQjRTRTtRW1c73tfUdbTTtRJ9rx24riltrZXuOtcQyWsJygkQbCCgelIeLR9afoU-nfYeU_w9Q57MwWcH42gDxDkbqphiktECyhPoUsw5wWCOyR9sejKUmEWyWQSaRaApkg2RZpFc5j6cD8zdAfrnqbPVAnw8AzY7Ow5FjvP5mVNaU65Z4T6fuL3f7R99AuMKCSlBLm7d3lC2BFeM839j_ZOV</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17272521</pqid></control><display><type>article</type><title>Human In vivo Dose-Response to Controlled, Low-Dose Low Linear Energy Transfer Ionizing Radiation Exposure</title><source>MEDLINE</source><source>American Association for Cancer Research Journals</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>GOLDBERG, Zelanna ; ROCKE, David M ; SCHWIETERT, Chad ; BERGLUND, Susanne R ; SANTANA, Alison ; JONES, Angela ; LEHMANN, Jbrg ; STERN, Robin ; RUIXIAO LU ; HARTMANN SIANTAR, Christine</creator><creatorcontrib>GOLDBERG, Zelanna ; ROCKE, David M ; SCHWIETERT, Chad ; BERGLUND, Susanne R ; SANTANA, Alison ; JONES, Angela ; LEHMANN, Jbrg ; STERN, Robin ; RUIXIAO LU ; HARTMANN SIANTAR, Christine</creatorcontrib><description>Purpose: The effect of low doses of low–linear energy transfer (photon) ionizing radiation (LDIR, <10 cGy) on human tissue when exposure
is under normal physiologic conditions is of significant interest to the medical and scientific community in therapeutic and
other contexts. Although, to date, there has been no direct assessment of the response of human tissue to LDIR when exposure
is under normal physiologic conditions of intact three-dimensional architecture, vasculature, and cell-cell contacts (between
epithelial cells and between epithelial and stromal cells).
Experimental Design: In this article, we present the first data on the response of human tissue exposed in vivo to LDIR with precisely controlled and calibrated doses. We evaluated transcriptomic responses to a single exposure of LDIR
in the normal skin of men undergoing therapeutic radiation for prostate cancer (research protocol, Health Insurance Portability
and Accountability Act–compliant, Institutional Review Board–approved). Using newly developed biostatistical tools that account
for individual splice variants and the expected variability of temporal response between humans even when the outcome is measured
at a single time, we show a dose-response pattern in gene expression in a number of pathways and gene groups that are biologically
plausible responses to LDIR.
Results: Examining genes and pathways identified as radiation-responsive in cell culture models, we found seven gene groups and five
pathways that were altered in men in this experiment. These included the Akt/phosphoinositide-3-kinase pathway, the growth
factor pathway, the stress/apoptosis pathway, and the pathway initiated by transforming growth factor-β signaling, whereas
gene groups with altered expression included the keratins, the zinc finger proteins and signaling molecules in the mitogen-activated
protein kinase gene group. We show that there is considerable individual variability in radiation response that makes the
detection of effects difficult, but still feasible when analyzed according to gene group and pathway.
Conclusions: These results show for the first time that low doses of radiation have an identifiable biosignature in human tissue, irradiated
in vivo with normal intact three-dimensional architecture, vascular supply, and innervation. The genes and pathways show that the
tissue ( a ) does detect the injury, ( b ) initiates a stress/inflammatory response, ( c ) undergoes DNA remodeling, as suggested by the significant increase in zinc finger protein gene expression, and ( d ) initiates a “pro-survival” response. The ability to detect a distinct radiation response pattern following LDIR exposure
has important implications for risk assessment in both therapeutic and national defense contexts.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-05-2625</identifier><identifier>PMID: 16778099</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antineoplastic agents ; Biological and medical sciences ; Biopsy ; Cell-cell interactions ; Chemokines - radiation effects ; Dose-Response Relationship, Radiation ; Gene Expression Regulation - radiation effects ; human solid tissue response ; Humans ; Inflammation ; Medical sciences ; Particle Accelerators ; Pharmacology. Drug treatments ; radiation ; Radiation, Ionizing ; Risk assessment ; RNA - genetics ; RNA - radiation effects ; Zinc Fingers - radiation effects</subject><ispartof>Clinical cancer research, 2006-06, Vol.12 (12), p.3723-3729</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-1b46ac6c3d61cb1b8674dd8cecb9c6c8878bbc905365e7c4e42f0e7d0043001a3</citedby><cites>FETCH-LOGICAL-c449t-1b46ac6c3d61cb1b8674dd8cecb9c6c8878bbc905365e7c4e42f0e7d0043001a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,3357,27926,27927</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17881382$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16778099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GOLDBERG, Zelanna</creatorcontrib><creatorcontrib>ROCKE, David M</creatorcontrib><creatorcontrib>SCHWIETERT, Chad</creatorcontrib><creatorcontrib>BERGLUND, Susanne R</creatorcontrib><creatorcontrib>SANTANA, Alison</creatorcontrib><creatorcontrib>JONES, Angela</creatorcontrib><creatorcontrib>LEHMANN, Jbrg</creatorcontrib><creatorcontrib>STERN, Robin</creatorcontrib><creatorcontrib>RUIXIAO LU</creatorcontrib><creatorcontrib>HARTMANN SIANTAR, Christine</creatorcontrib><title>Human In vivo Dose-Response to Controlled, Low-Dose Low Linear Energy Transfer Ionizing Radiation Exposure</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The effect of low doses of low–linear energy transfer (photon) ionizing radiation (LDIR, <10 cGy) on human tissue when exposure
is under normal physiologic conditions is of significant interest to the medical and scientific community in therapeutic and
other contexts. Although, to date, there has been no direct assessment of the response of human tissue to LDIR when exposure
is under normal physiologic conditions of intact three-dimensional architecture, vasculature, and cell-cell contacts (between
epithelial cells and between epithelial and stromal cells).
Experimental Design: In this article, we present the first data on the response of human tissue exposed in vivo to LDIR with precisely controlled and calibrated doses. We evaluated transcriptomic responses to a single exposure of LDIR
in the normal skin of men undergoing therapeutic radiation for prostate cancer (research protocol, Health Insurance Portability
and Accountability Act–compliant, Institutional Review Board–approved). Using newly developed biostatistical tools that account
for individual splice variants and the expected variability of temporal response between humans even when the outcome is measured
at a single time, we show a dose-response pattern in gene expression in a number of pathways and gene groups that are biologically
plausible responses to LDIR.
Results: Examining genes and pathways identified as radiation-responsive in cell culture models, we found seven gene groups and five
pathways that were altered in men in this experiment. These included the Akt/phosphoinositide-3-kinase pathway, the growth
factor pathway, the stress/apoptosis pathway, and the pathway initiated by transforming growth factor-β signaling, whereas
gene groups with altered expression included the keratins, the zinc finger proteins and signaling molecules in the mitogen-activated
protein kinase gene group. We show that there is considerable individual variability in radiation response that makes the
detection of effects difficult, but still feasible when analyzed according to gene group and pathway.
Conclusions: These results show for the first time that low doses of radiation have an identifiable biosignature in human tissue, irradiated
in vivo with normal intact three-dimensional architecture, vascular supply, and innervation. The genes and pathways show that the
tissue ( a ) does detect the injury, ( b ) initiates a stress/inflammatory response, ( c ) undergoes DNA remodeling, as suggested by the significant increase in zinc finger protein gene expression, and ( d ) initiates a “pro-survival” response. The ability to detect a distinct radiation response pattern following LDIR exposure
has important implications for risk assessment in both therapeutic and national defense contexts.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cell-cell interactions</subject><subject>Chemokines - radiation effects</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Gene Expression Regulation - radiation effects</subject><subject>human solid tissue response</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Medical sciences</subject><subject>Particle Accelerators</subject><subject>Pharmacology. Drug treatments</subject><subject>radiation</subject><subject>Radiation, Ionizing</subject><subject>Risk assessment</subject><subject>RNA - genetics</subject><subject>RNA - radiation effects</subject><subject>Zinc Fingers - radiation effects</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkG1rFDEQgIMotlZ_gpIvCoJb87rJfizraQ8OhKN-Dtns7F3KXnImu63115vlTgoDMwzPzDAPQu8puaZU6q-UKF0Rwdl1224rIitWM_kCXVIpVcVZLV-W-j9zgd7kfE8IFZSI1-iC1kpp0jSX6P52PtiA1wE_-IeIv8UM1RbyMYYMeIq4jWFKcRyh_4I38bFagKXAGx_AJrwKkHZP-C7ZkAdIeB2D_-vDDm9t7-3kY8CrP8eY5wRv0avBjhnenfMV-vV9ddfeVpufP9btzaZyQjRTRTtRW1c73tfUdbTTtRJ9rx24riltrZXuOtcQyWsJygkQbCCgelIeLR9afoU-nfYeU_w9Q57MwWcH42gDxDkbqphiktECyhPoUsw5wWCOyR9sejKUmEWyWQSaRaApkg2RZpFc5j6cD8zdAfrnqbPVAnw8AzY7Ow5FjvP5mVNaU65Z4T6fuL3f7R99AuMKCSlBLm7d3lC2BFeM839j_ZOV</recordid><startdate>20060615</startdate><enddate>20060615</enddate><creator>GOLDBERG, Zelanna</creator><creator>ROCKE, David M</creator><creator>SCHWIETERT, Chad</creator><creator>BERGLUND, Susanne R</creator><creator>SANTANA, Alison</creator><creator>JONES, Angela</creator><creator>LEHMANN, Jbrg</creator><creator>STERN, Robin</creator><creator>RUIXIAO LU</creator><creator>HARTMANN SIANTAR, Christine</creator><general>American Association for Cancer Research</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><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20060615</creationdate><title>Human In vivo Dose-Response to Controlled, Low-Dose Low Linear Energy Transfer Ionizing Radiation Exposure</title><author>GOLDBERG, Zelanna ; ROCKE, David M ; SCHWIETERT, Chad ; BERGLUND, Susanne R ; SANTANA, Alison ; JONES, Angela ; LEHMANN, Jbrg ; STERN, Robin ; RUIXIAO LU ; HARTMANN SIANTAR, Christine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-1b46ac6c3d61cb1b8674dd8cecb9c6c8878bbc905365e7c4e42f0e7d0043001a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Cell-cell interactions</topic><topic>Chemokines - radiation effects</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Gene Expression Regulation - radiation effects</topic><topic>human solid tissue response</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Medical sciences</topic><topic>Particle Accelerators</topic><topic>Pharmacology. Drug treatments</topic><topic>radiation</topic><topic>Radiation, Ionizing</topic><topic>Risk assessment</topic><topic>RNA - genetics</topic><topic>RNA - radiation effects</topic><topic>Zinc Fingers - radiation effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GOLDBERG, Zelanna</creatorcontrib><creatorcontrib>ROCKE, David M</creatorcontrib><creatorcontrib>SCHWIETERT, Chad</creatorcontrib><creatorcontrib>BERGLUND, Susanne R</creatorcontrib><creatorcontrib>SANTANA, Alison</creatorcontrib><creatorcontrib>JONES, Angela</creatorcontrib><creatorcontrib>LEHMANN, Jbrg</creatorcontrib><creatorcontrib>STERN, Robin</creatorcontrib><creatorcontrib>RUIXIAO LU</creatorcontrib><creatorcontrib>HARTMANN SIANTAR, Christine</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><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GOLDBERG, Zelanna</au><au>ROCKE, David M</au><au>SCHWIETERT, Chad</au><au>BERGLUND, Susanne R</au><au>SANTANA, Alison</au><au>JONES, Angela</au><au>LEHMANN, Jbrg</au><au>STERN, Robin</au><au>RUIXIAO LU</au><au>HARTMANN SIANTAR, Christine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human In vivo Dose-Response to Controlled, Low-Dose Low Linear Energy Transfer Ionizing Radiation Exposure</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2006-06-15</date><risdate>2006</risdate><volume>12</volume><issue>12</issue><spage>3723</spage><epage>3729</epage><pages>3723-3729</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: The effect of low doses of low–linear energy transfer (photon) ionizing radiation (LDIR, <10 cGy) on human tissue when exposure
is under normal physiologic conditions is of significant interest to the medical and scientific community in therapeutic and
other contexts. Although, to date, there has been no direct assessment of the response of human tissue to LDIR when exposure
is under normal physiologic conditions of intact three-dimensional architecture, vasculature, and cell-cell contacts (between
epithelial cells and between epithelial and stromal cells).
Experimental Design: In this article, we present the first data on the response of human tissue exposed in vivo to LDIR with precisely controlled and calibrated doses. We evaluated transcriptomic responses to a single exposure of LDIR
in the normal skin of men undergoing therapeutic radiation for prostate cancer (research protocol, Health Insurance Portability
and Accountability Act–compliant, Institutional Review Board–approved). Using newly developed biostatistical tools that account
for individual splice variants and the expected variability of temporal response between humans even when the outcome is measured
at a single time, we show a dose-response pattern in gene expression in a number of pathways and gene groups that are biologically
plausible responses to LDIR.
Results: Examining genes and pathways identified as radiation-responsive in cell culture models, we found seven gene groups and five
pathways that were altered in men in this experiment. These included the Akt/phosphoinositide-3-kinase pathway, the growth
factor pathway, the stress/apoptosis pathway, and the pathway initiated by transforming growth factor-β signaling, whereas
gene groups with altered expression included the keratins, the zinc finger proteins and signaling molecules in the mitogen-activated
protein kinase gene group. We show that there is considerable individual variability in radiation response that makes the
detection of effects difficult, but still feasible when analyzed according to gene group and pathway.
Conclusions: These results show for the first time that low doses of radiation have an identifiable biosignature in human tissue, irradiated
in vivo with normal intact three-dimensional architecture, vascular supply, and innervation. The genes and pathways show that the
tissue ( a ) does detect the injury, ( b ) initiates a stress/inflammatory response, ( c ) undergoes DNA remodeling, as suggested by the significant increase in zinc finger protein gene expression, and ( d ) initiates a “pro-survival” response. The ability to detect a distinct radiation response pattern following LDIR exposure
has important implications for risk assessment in both therapeutic and national defense contexts.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16778099</pmid><doi>10.1158/1078-0432.CCR-05-2625</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2006-06, Vol.12 (12), p.3723-3729 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17272521 |
| source | MEDLINE; American Association for Cancer Research Journals; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Antineoplastic agents Biological and medical sciences Biopsy Cell-cell interactions Chemokines - radiation effects Dose-Response Relationship, Radiation Gene Expression Regulation - radiation effects human solid tissue response Humans Inflammation Medical sciences Particle Accelerators Pharmacology. Drug treatments radiation Radiation, Ionizing Risk assessment RNA - genetics RNA - radiation effects Zinc Fingers - radiation effects |
| title | Human In vivo Dose-Response to Controlled, Low-Dose Low Linear Energy Transfer Ionizing Radiation Exposure |
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