Low Dose Radiation Causes Skin Cancer in Mice and Has a Differential Effect on Distinct Epidermal Stem Cells
The carcinogenic effect of ionizing radiation has been evaluated based on limited populations accidently exposed to high dose radiation. In contrast, insufficient data are available on the effect of low dose radiation (LDR), such as radiation deriving from medical investigations and interventions, a...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2017-05, Vol.35 (5), p.1355-1364 |
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| creator | Revenco, Tatiana Lapouge, Gaelle Moers, Virginie Brohée, Sylvain Sotiropoulou, Panagiota A. |
| description | The carcinogenic effect of ionizing radiation has been evaluated based on limited populations accidently exposed to high dose radiation. In contrast, insufficient data are available on the effect of low dose radiation (LDR), such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that LDR results in DNA damage in sebaceous gland (SG) and bulge epidermal stem cells (SCs). While the first commit apoptosis upon low dose irradiation, the latter survive. Bulge SC survival coincides with higher HIF‐1α expression and a metabolic switch upon LDR. Knocking down HIF‐1α sensitizes bulge SCs to LDR‐induced apoptosis, while upregulation of HIF‐1α in the epidermis, including SG SCs, rescues cell death. Most importantly, we show that LDR results in cancer formation with full penetrance in the radiation‐sensitive Patched1 heterozygous mice. Overall, our results demonstrate for the first time that LDR can be a potent carcinogen in individuals predisposed to cancer. Stem Cells 2017;35:1355–1364 |
| doi_str_mv | 10.1002/stem.2571 |
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In contrast, insufficient data are available on the effect of low dose radiation (LDR), such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that LDR results in DNA damage in sebaceous gland (SG) and bulge epidermal stem cells (SCs). While the first commit apoptosis upon low dose irradiation, the latter survive. Bulge SC survival coincides with higher HIF‐1α expression and a metabolic switch upon LDR. Knocking down HIF‐1α sensitizes bulge SCs to LDR‐induced apoptosis, while upregulation of HIF‐1α in the epidermis, including SG SCs, rescues cell death. Most importantly, we show that LDR results in cancer formation with full penetrance in the radiation‐sensitive Patched1 heterozygous mice. Overall, our results demonstrate for the first time that LDR can be a potent carcinogen in individuals predisposed to cancer. 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In contrast, insufficient data are available on the effect of low dose radiation (LDR), such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that LDR results in DNA damage in sebaceous gland (SG) and bulge epidermal stem cells (SCs). While the first commit apoptosis upon low dose irradiation, the latter survive. Bulge SC survival coincides with higher HIF‐1α expression and a metabolic switch upon LDR. Knocking down HIF‐1α sensitizes bulge SCs to LDR‐induced apoptosis, while upregulation of HIF‐1α in the epidermis, including SG SCs, rescues cell death. Most importantly, we show that LDR results in cancer formation with full penetrance in the radiation‐sensitive Patched1 heterozygous mice. Overall, our results demonstrate for the first time that LDR can be a potent carcinogen in individuals predisposed to cancer. Stem Cells 2017;35:1355–1364</description><subject>Adult stem cells</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>Carcinogens</subject><subject>Carcinoma, Basal Cell - pathology</subject><subject>Cell death</subject><subject>Cell Survival - radiation effects</subject><subject>Damage</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Epidermis</subject><subject>Epidermis - radiation effects</subject><subject>Exposure</subject><subject>Health risks</subject><subject>Heterozygote</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Hypoxia-inducible factor 1a</subject><subject>Ionizing radiation</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Occupational exposure</subject><subject>Occupational health</subject><subject>Patched-1 Receptor - metabolism</subject><subject>Penetrance</subject><subject>Populations</subject><subject>Radiation</subject><subject>Sebaceous gland</subject><subject>Sebaceous Glands - pathology</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - etiology</subject><subject>Skin Neoplasms - pathology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Stem Cells - radiation effects</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1LwzAYhYMoOj8u_AMS8EYv6pK0aZNL2aYTJoLT65ImbyHaj5m0jP17Uze9EMSrPJDnPRw4CJ1TckMJYWPfQX3DeEb30IjyREaJpGI_MEnTiBMpj9Cx92-E0IQLcYiOmAh3JJYjVC3aNZ62HvCzMlZ1tm3wRPUePF6-24EbDQ4HerQasGoMniuPFZ7asgQHTWdVhWeBdYfD7dT6zjaBZytrwNXhcxna4QlUlT9FB6WqPJzt3hP0ejd7mcyjxdP9w-R2EekkNI8gyQhkICSjShZGFIICM1JlJCUamEyNIVwTpUBRJjIwWsVQSGIEKXiZpfEJutrmrlz70YPv8tp6HRqoBtre51TILM5omg7q5S_1re1dE9oNFhcx51L-Y1EmY87iYF1vLe1a7x2U-crZWrlNTkk-DJUPQ-XDUMG92CX2RQ3mx_xeJgjjrbC2FWz-TsqXL7PHr8hP7gGbUQ</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Revenco, Tatiana</creator><creator>Lapouge, Gaelle</creator><creator>Moers, Virginie</creator><creator>Brohée, Sylvain</creator><creator>Sotiropoulou, Panagiota A.</creator><general>Oxford University Press</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201705</creationdate><title>Low Dose Radiation Causes Skin Cancer in Mice and Has a Differential Effect on Distinct Epidermal Stem Cells</title><author>Revenco, Tatiana ; Lapouge, Gaelle ; Moers, Virginie ; Brohée, Sylvain ; Sotiropoulou, Panagiota A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4491-e470e7e8921a9bd8b81e2d9a7060ce296dd05c0aaea1287edca3eb90d80b5f763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult stem cells</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cancer</topic><topic>Carcinogens</topic><topic>Carcinoma, Basal Cell - pathology</topic><topic>Cell death</topic><topic>Cell Survival - radiation effects</topic><topic>Damage</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Epidermis</topic><topic>Epidermis - radiation effects</topic><topic>Exposure</topic><topic>Health risks</topic><topic>Heterozygote</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Hypoxia-inducible factor 1a</topic><topic>Ionizing radiation</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Occupational exposure</topic><topic>Occupational health</topic><topic>Patched-1 Receptor - metabolism</topic><topic>Penetrance</topic><topic>Populations</topic><topic>Radiation</topic><topic>Sebaceous gland</topic><topic>Sebaceous Glands - pathology</topic><topic>Skin cancer</topic><topic>Skin Neoplasms - etiology</topic><topic>Skin Neoplasms - pathology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Stem Cells - radiation effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Revenco, Tatiana</creatorcontrib><creatorcontrib>Lapouge, Gaelle</creatorcontrib><creatorcontrib>Moers, Virginie</creatorcontrib><creatorcontrib>Brohée, Sylvain</creatorcontrib><creatorcontrib>Sotiropoulou, Panagiota A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Revenco, Tatiana</au><au>Lapouge, Gaelle</au><au>Moers, Virginie</au><au>Brohée, Sylvain</au><au>Sotiropoulou, Panagiota A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low Dose Radiation Causes Skin Cancer in Mice and Has a Differential Effect on Distinct Epidermal Stem Cells</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2017-05</date><risdate>2017</risdate><volume>35</volume><issue>5</issue><spage>1355</spage><epage>1364</epage><pages>1355-1364</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>The carcinogenic effect of ionizing radiation has been evaluated based on limited populations accidently exposed to high dose radiation. In contrast, insufficient data are available on the effect of low dose radiation (LDR), such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that LDR results in DNA damage in sebaceous gland (SG) and bulge epidermal stem cells (SCs). While the first commit apoptosis upon low dose irradiation, the latter survive. Bulge SC survival coincides with higher HIF‐1α expression and a metabolic switch upon LDR. Knocking down HIF‐1α sensitizes bulge SCs to LDR‐induced apoptosis, while upregulation of HIF‐1α in the epidermis, including SG SCs, rescues cell death. Most importantly, we show that LDR results in cancer formation with full penetrance in the radiation‐sensitive Patched1 heterozygous mice. Overall, our results demonstrate for the first time that LDR can be a potent carcinogen in individuals predisposed to cancer. 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| subjects | Adult stem cells Animals Apoptosis Cancer Carcinogens Carcinoma, Basal Cell - pathology Cell death Cell Survival - radiation effects Damage Deoxyribonucleic acid DNA DNA Damage Dose-Response Relationship, Radiation Epidermis Epidermis - radiation effects Exposure Health risks Heterozygote Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Hypoxia-inducible factor 1a Ionizing radiation Metabolism Mice Occupational exposure Occupational health Patched-1 Receptor - metabolism Penetrance Populations Radiation Sebaceous gland Sebaceous Glands - pathology Skin cancer Skin Neoplasms - etiology Skin Neoplasms - pathology Stem cell transplantation Stem cells Stem Cells - metabolism Stem Cells - radiation effects |
| title | Low Dose Radiation Causes Skin Cancer in Mice and Has a Differential Effect on Distinct Epidermal Stem Cells |
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