Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin
Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen...
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description | Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer. |
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Peter</contributor><creatorcontrib>Thompson, Benjamin C ; Halliday, Gary M ; Damian, Diona L ; Soyer, H. Peter</creatorcontrib><description>Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0117491</identifier><identifier>PMID: 25658450</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Arsenic ; Arsenic compounds ; Arsenite ; Arsenites - pharmacology ; Cancer ; Carcinogens ; Cell Line ; Chemotherapy ; Computer simulation ; Contamination ; Cyclobutane ; Cyclobutane pyrimidine dimers ; Damage prevention ; Deoxyguanosine ; Deoxyribonucleic acid ; Dimers ; DNA ; DNA damage ; DNA Damage - drug effects ; DNA Damage - radiation effects ; DNA repair ; DNA Repair - drug effects ; Exposure ; Global health ; Health risks ; Humans ; Immunofluorescence ; Keratinocytes ; Keratinocytes - drug effects ; Keratinocytes - radiation effects ; Niacinamide ; Niacinamide - pharmacology ; Nicotinamide ; Nicotinic acid ; Radiation damage ; Radiation effects ; Repair ; Skin ; Skin - drug effects ; Skin - radiation effects ; Skin cancer ; Skin diseases ; Sodium ; Sodium arsenite ; Sodium Compounds - pharmacology ; Supplements ; Ultraviolet radiation ; Ultraviolet Rays ; Water pollution ; Water sources ; Wound Healing - drug effects</subject><ispartof>PloS one, 2015-02, Vol.10 (2), p.e0117491</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Thompson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Thompson et al 2015 Thompson et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a3a32244ebce70d33d810254c1c9d6dace02961eafbda6859c97c1babfb92a263</citedby><cites>FETCH-LOGICAL-c692t-a3a32244ebce70d33d810254c1c9d6dace02961eafbda6859c97c1babfb92a263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319842/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319842/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25658450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Soyer, H. Peter</contributor><creatorcontrib>Thompson, Benjamin C</creatorcontrib><creatorcontrib>Halliday, Gary M</creatorcontrib><creatorcontrib>Damian, Diona L</creatorcontrib><title>Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.</description><subject>Arsenic</subject><subject>Arsenic compounds</subject><subject>Arsenite</subject><subject>Arsenites - pharmacology</subject><subject>Cancer</subject><subject>Carcinogens</subject><subject>Cell Line</subject><subject>Chemotherapy</subject><subject>Computer simulation</subject><subject>Contamination</subject><subject>Cyclobutane</subject><subject>Cyclobutane pyrimidine dimers</subject><subject>Damage prevention</subject><subject>Deoxyguanosine</subject><subject>Deoxyribonucleic acid</subject><subject>Dimers</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA Damage - drug effects</subject><subject>DNA Damage - radiation effects</subject><subject>DNA repair</subject><subject>DNA Repair - drug effects</subject><subject>Exposure</subject><subject>Global health</subject><subject>Health risks</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Keratinocytes</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - radiation effects</subject><subject>Niacinamide</subject><subject>Niacinamide - pharmacology</subject><subject>Nicotinamide</subject><subject>Nicotinic acid</subject><subject>Radiation damage</subject><subject>Radiation effects</subject><subject>Repair</subject><subject>Skin</subject><subject>Skin - drug effects</subject><subject>Skin - radiation effects</subject><subject>Skin cancer</subject><subject>Skin diseases</subject><subject>Sodium</subject><subject>Sodium arsenite</subject><subject>Sodium Compounds - pharmacology</subject><subject>Supplements</subject><subject>Ultraviolet radiation</subject><subject>Ultraviolet Rays</subject><subject>Water pollution</subject><subject>Water sources</subject><subject>Wound Healing - drug effects</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-LEzEUxQdR3HX1G4gGBMGH1kkyk05ehFL_bGHZBV19DXeSO226M0lNZsruq5_c1HaXFhQkDwnJ757cnJwse0nzMeUT-n7lh-CgHa-9w3FO6aSQ9FF2SiVnI8Fy_vhgfZI9i3GV5yWvhHianbBSlFVR5qfZr0urfW8ddNYgQbcEpzGSgGuwgfiGQIjorCbgDBnaPsDG-hZ7EsBY6K13I-vMoNGQj5dTYqCDBRLryDnM4JrcYEiQ8_quT6pbDbwlG7vxZDl04Ei8se559qSBNuKL_XyWff_86Xp2Prq4-jKfTS9GWkjWj4ADZ6wosNY4yQ3npqI5KwtNtTTCgMacSUERmtqAqEqp5UTTGuqmlgyY4GfZ653uuvVR7e2LioqSUSkqIRMx3xHGw0qtg-0g3CkPVv3Z8GGhIPRWt6iSfMNriUIIXlSlqSdUp-ZYrouqYWWZtD7sbxvqDo1Gl7xrj0SPT5xdqoXfqIJTWRUsCbzZCwT_c8DY_6PlPbWA1JV1jU9iurNRq2nBZJViQbdPH_-FSsNgl_7fYWPT_lHBu6OCxPR42y9giFHNv339f_bqxzH79oBdIrT9Mvp22AYpHoPFDtTBxxiweXCO5mqb_3s31Db_ap__VPbq0PWHovvA89_QUgHl</recordid><startdate>20150206</startdate><enddate>20150206</enddate><creator>Thompson, Benjamin C</creator><creator>Halliday, Gary M</creator><creator>Damian, Diona L</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150206</creationdate><title>Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin</title><author>Thompson, Benjamin C ; Halliday, Gary M ; Damian, Diona L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a3a32244ebce70d33d810254c1c9d6dace02961eafbda6859c97c1babfb92a263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Arsenic</topic><topic>Arsenic compounds</topic><topic>Arsenite</topic><topic>Arsenites - pharmacology</topic><topic>Cancer</topic><topic>Carcinogens</topic><topic>Cell Line</topic><topic>Chemotherapy</topic><topic>Computer simulation</topic><topic>Contamination</topic><topic>Cyclobutane</topic><topic>Cyclobutane pyrimidine dimers</topic><topic>Damage prevention</topic><topic>Deoxyguanosine</topic><topic>Deoxyribonucleic acid</topic><topic>Dimers</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA Damage - drug effects</topic><topic>DNA Damage - radiation effects</topic><topic>DNA repair</topic><topic>DNA Repair - drug effects</topic><topic>Exposure</topic><topic>Global health</topic><topic>Health risks</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Keratinocytes</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - radiation effects</topic><topic>Niacinamide</topic><topic>Niacinamide - pharmacology</topic><topic>Nicotinamide</topic><topic>Nicotinic acid</topic><topic>Radiation damage</topic><topic>Radiation effects</topic><topic>Repair</topic><topic>Skin</topic><topic>Skin - drug effects</topic><topic>Skin - radiation effects</topic><topic>Skin cancer</topic><topic>Skin diseases</topic><topic>Sodium</topic><topic>Sodium arsenite</topic><topic>Sodium Compounds - pharmacology</topic><topic>Supplements</topic><topic>Ultraviolet radiation</topic><topic>Ultraviolet Rays</topic><topic>Water pollution</topic><topic>Water sources</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thompson, Benjamin C</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>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-02-06</date><risdate>2015</risdate><volume>10</volume><issue>2</issue><spage>e0117491</spage><pages>e0117491-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25658450</pmid><doi>10.1371/journal.pone.0117491</doi><tpages>e0117491</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Arsenic Arsenic compounds Arsenite Arsenites - pharmacology Cancer Carcinogens Cell Line Chemotherapy Computer simulation Contamination Cyclobutane Cyclobutane pyrimidine dimers Damage prevention Deoxyguanosine Deoxyribonucleic acid Dimers DNA DNA damage DNA Damage - drug effects DNA Damage - radiation effects DNA repair DNA Repair - drug effects Exposure Global health Health risks Humans Immunofluorescence Keratinocytes Keratinocytes - drug effects Keratinocytes - radiation effects Niacinamide Niacinamide - pharmacology Nicotinamide Nicotinic acid Radiation damage Radiation effects Repair Skin Skin - drug effects Skin - radiation effects Skin cancer Skin diseases Sodium Sodium arsenite Sodium Compounds - pharmacology Supplements Ultraviolet radiation Ultraviolet Rays Water pollution Water sources Wound Healing - drug effects |
title | Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin |
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