Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin
Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly r...
Gespeichert in:
Veröffentlicht in: | Carcinogenesis (New York) 2013-05, Vol.34 (5), p.1144-1149 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1149 |
---|---|
container_issue | 5 |
container_start_page | 1144 |
container_title | Carcinogenesis (New York) |
container_volume | 34 |
creator | Surjana, Devita Halliday, Gary M Damian, Diona L |
description | Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention. |
doi_str_mv | 10.1093/carcin/bgt017 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1367486871</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1367486871</sourcerecordid><originalsourceid>FETCH-LOGICAL-c365t-ba06724169904abaf191531c53aeba408ca0ca424448f067bf14d69e39d5bf2c3</originalsourceid><addsrcrecordid>eNqNkT1PwzAQQC0EglIYWZFHllA7dtJ4rPiWUFlgji72pTUkdrGTiv57glKY0Q0nnZ7ecI-QC86uOVNipiFo62bVqmN8fkAmXOYsSXnBDsmEcSkSIYQ8IacxvjPGc5GpY3KSDjfFeDohm6XVvrMOWmuQoluD0xhpwA3YQH1N-6YLsLW-wY4GMBY6611inek1Gnq7XFADLayQWkfXfQuOfmAYIOf1rhtM4AzFL7q1W0_jh3Vn5KiGJuL5fk_J2_3d681j8vzy8HSzeE60yLMuqYDl81TyXCkmoYKaK54JrjMBWIFkhQamQaZSyqIe0Krm0uQKhTJZVadaTMnV6N0E_9lj7MrWRo1NAw59H0su8rks8mLO_4EOz1LpMAOajKgOPsaAdbkJtoWwKzkrf3qUY49y7DHwl3t1X7Vo_ujfAOIb3W-JIg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1349092929</pqid></control><display><type>article</type><title>Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Surjana, Devita ; Halliday, Gary M ; Damian, Diona L</creator><creatorcontrib>Surjana, Devita ; Halliday, Gary M ; Damian, Diona L</creatorcontrib><description>Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgt017</identifier><identifier>PMID: 23349012</identifier><language>eng</language><publisher>England</publisher><subject>ATP ; Cell Line ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - metabolism ; DNA - biosynthesis ; DNA - drug effects ; DNA - radiation effects ; DNA Damage ; DNA Glycosylases ; DNA Repair ; Humans ; Keratinocytes - drug effects ; Keratinocytes - radiation effects ; Niacinamide - pharmacology ; Pyrimidine Dimers - metabolism ; Skin - drug effects ; Skin - metabolism ; Skin - radiation effects ; Skin Neoplasms - metabolism ; Skin Neoplasms - prevention & control ; Ultraviolet Rays - adverse effects</subject><ispartof>Carcinogenesis (New York), 2013-05, Vol.34 (5), p.1144-1149</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-ba06724169904abaf191531c53aeba408ca0ca424448f067bf14d69e39d5bf2c3</citedby><cites>FETCH-LOGICAL-c365t-ba06724169904abaf191531c53aeba408ca0ca424448f067bf14d69e39d5bf2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23349012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Surjana, Devita</creatorcontrib><creatorcontrib>Halliday, Gary M</creatorcontrib><creatorcontrib>Damian, Diona L</creatorcontrib><title>Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.</description><subject>ATP</subject><subject>Cell Line</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - metabolism</subject><subject>DNA - biosynthesis</subject><subject>DNA - drug effects</subject><subject>DNA - radiation effects</subject><subject>DNA Damage</subject><subject>DNA Glycosylases</subject><subject>DNA Repair</subject><subject>Humans</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - radiation effects</subject><subject>Niacinamide - pharmacology</subject><subject>Pyrimidine Dimers - metabolism</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - radiation effects</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - prevention & control</subject><subject>Ultraviolet Rays - adverse effects</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkT1PwzAQQC0EglIYWZFHllA7dtJ4rPiWUFlgji72pTUkdrGTiv57glKY0Q0nnZ7ecI-QC86uOVNipiFo62bVqmN8fkAmXOYsSXnBDsmEcSkSIYQ8IacxvjPGc5GpY3KSDjfFeDohm6XVvrMOWmuQoluD0xhpwA3YQH1N-6YLsLW-wY4GMBY6611inek1Gnq7XFADLayQWkfXfQuOfmAYIOf1rhtM4AzFL7q1W0_jh3Vn5KiGJuL5fk_J2_3d681j8vzy8HSzeE60yLMuqYDl81TyXCkmoYKaK54JrjMBWIFkhQamQaZSyqIe0Krm0uQKhTJZVadaTMnV6N0E_9lj7MrWRo1NAw59H0su8rks8mLO_4EOz1LpMAOajKgOPsaAdbkJtoWwKzkrf3qUY49y7DHwl3t1X7Vo_ujfAOIb3W-JIg</recordid><startdate>201305</startdate><enddate>201305</enddate><creator>Surjana, Devita</creator><creator>Halliday, Gary M</creator><creator>Damian, Diona L</creator><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><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>201305</creationdate><title>Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin</title><author>Surjana, Devita ; Halliday, Gary M ; Damian, Diona L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-ba06724169904abaf191531c53aeba408ca0ca424448f067bf14d69e39d5bf2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>ATP</topic><topic>Cell Line</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - metabolism</topic><topic>DNA - biosynthesis</topic><topic>DNA - drug effects</topic><topic>DNA - radiation effects</topic><topic>DNA Damage</topic><topic>DNA Glycosylases</topic><topic>DNA Repair</topic><topic>Humans</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - radiation effects</topic><topic>Niacinamide - pharmacology</topic><topic>Pyrimidine Dimers - metabolism</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - radiation effects</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - prevention & control</topic><topic>Ultraviolet Rays - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Surjana, Devita</creatorcontrib><creatorcontrib>Halliday, Gary M</creatorcontrib><creatorcontrib>Damian, Diona L</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><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Surjana, Devita</au><au>Halliday, Gary M</au><au>Damian, Diona L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2013-05</date><risdate>2013</risdate><volume>34</volume><issue>5</issue><spage>1144</spage><epage>1149</epage><pages>1144-1149</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><abstract>Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.</abstract><cop>England</cop><pmid>23349012</pmid><doi>10.1093/carcin/bgt017</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0143-3334 |
ispartof | Carcinogenesis (New York), 2013-05, Vol.34 (5), p.1144-1149 |
issn | 0143-3334 1460-2180 |
language | eng |
recordid | cdi_proquest_miscellaneous_1367486871 |
source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | ATP Cell Line Deoxyguanosine - analogs & derivatives Deoxyguanosine - metabolism DNA - biosynthesis DNA - drug effects DNA - radiation effects DNA Damage DNA Glycosylases DNA Repair Humans Keratinocytes - drug effects Keratinocytes - radiation effects Niacinamide - pharmacology Pyrimidine Dimers - metabolism Skin - drug effects Skin - metabolism Skin - radiation effects Skin Neoplasms - metabolism Skin Neoplasms - prevention & control Ultraviolet Rays - adverse effects |
title | Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T18%3A42%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nicotinamide%20enhances%20repair%20of%20ultraviolet%20radiation-induced%20DNA%20damage%20in%20human%20keratinocytes%20and%20ex%20vivo%20skin&rft.jtitle=Carcinogenesis%20(New%20York)&rft.au=Surjana,%20Devita&rft.date=2013-05&rft.volume=34&rft.issue=5&rft.spage=1144&rft.epage=1149&rft.pages=1144-1149&rft.issn=0143-3334&rft.eissn=1460-2180&rft_id=info:doi/10.1093/carcin/bgt017&rft_dat=%3Cproquest_cross%3E1367486871%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1349092929&rft_id=info:pmid/23349012&rfr_iscdi=true |