Accelerated repair and reduced mutagenicity of DNA damage induced by cigarette smoke in human bronchial cells transfected with E.coli formamidopyrimidine DNA glycosylase
Cigarette smoke (CS) is associated to a number of pathologies including lung cancer. Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH) inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimid...
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| description | Cigarette smoke (CS) is associated to a number of pathologies including lung cancer. Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH) inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG) repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP). Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na(+)K(+)-ATPase locus (oua(r)) were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells' capacity to repair damaged DNA. |
| doi_str_mv | 10.1371/journal.pone.0087984 |
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Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH) inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG) repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP). Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na(+)K(+)-ATPase locus (oua(r)) were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells' capacity to repair damaged DNA.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0087984</identifier><identifier>PMID: 24498234</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adducts ; Bacteria ; Biology ; Bronchi - metabolism ; Bronchi - pathology ; Carcinogens ; Cell adhesion & migration ; Cell Line, Tumor ; Cigarette smoke ; Cigarettes ; Cloning ; Condensates ; Conditioned stimulus ; Damage ; Deoxyribonucleic acid ; DNA ; DNA adducts ; DNA Damage ; DNA glycosylase ; DNA Repair ; DNA-Formamidopyrimidine Glycosylase - biosynthesis ; DNA-Formamidopyrimidine Glycosylase - genetics ; E coli ; Enzymes ; Escherichia coli - enzymology ; Escherichia coli - genetics ; Escherichia coli Proteins - biosynthesis ; Escherichia coli Proteins - genetics ; Female ; Fluorescence ; Fusion protein ; Gene expression ; Genetic vectors ; Green fluorescent protein ; Health sciences ; Humans ; Ionizing radiation ; Kinases ; Low concentrations ; Lung cancer ; Lung carcinoma ; Lung diseases ; Lungs ; Maintenance ; Medical research ; Medicine ; Middle Aged ; Mutagenesis ; Mutagenicity ; Mutation ; Na+/K+-exchanging ATPase ; Non-small cell lung cancer ; Non-small cell lung carcinoma ; Oxygen ; Polycyclic aromatic hydrocarbons ; Proteins ; Reactive oxygen species ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - genetics ; Repair ; Small cell lung carcinoma ; Smoke ; Smoking ; Tobacco Smoke Pollution - adverse effects ; Transfection</subject><ispartof>PloS one, 2014-01, Vol.9 (1), p.e87984</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Foresta 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. 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Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH) inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG) repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP). Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na(+)K(+)-ATPase locus (oua(r)) were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells' capacity to repair damaged DNA.</description><subject>Adducts</subject><subject>Bacteria</subject><subject>Biology</subject><subject>Bronchi - metabolism</subject><subject>Bronchi - pathology</subject><subject>Carcinogens</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cigarette smoke</subject><subject>Cigarettes</subject><subject>Cloning</subject><subject>Condensates</subject><subject>Conditioned stimulus</subject><subject>Damage</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA adducts</subject><subject>DNA Damage</subject><subject>DNA glycosylase</subject><subject>DNA Repair</subject><subject>DNA-Formamidopyrimidine Glycosylase - biosynthesis</subject><subject>DNA-Formamidopyrimidine Glycosylase - genetics</subject><subject>E coli</subject><subject>Enzymes</subject><subject>Escherichia coli - enzymology</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli Proteins - biosynthesis</subject><subject>Escherichia coli Proteins - genetics</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Fusion protein</subject><subject>Gene expression</subject><subject>Genetic vectors</subject><subject>Green fluorescent protein</subject><subject>Health sciences</subject><subject>Humans</subject><subject>Ionizing radiation</subject><subject>Kinases</subject><subject>Low concentrations</subject><subject>Lung cancer</subject><subject>Lung carcinoma</subject><subject>Lung diseases</subject><subject>Lungs</subject><subject>Maintenance</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mutagenesis</subject><subject>Mutagenicity</subject><subject>Mutation</subject><subject>Na+/K+-exchanging ATPase</subject><subject>Non-small cell lung cancer</subject><subject>Non-small cell lung carcinoma</subject><subject>Oxygen</subject><subject>Polycyclic aromatic hydrocarbons</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - genetics</subject><subject>Repair</subject><subject>Small cell lung carcinoma</subject><subject>Smoke</subject><subject>Smoking</subject><subject>Tobacco Smoke Pollution - adverse effects</subject><subject>Transfection</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9uKFDEQhhtR3HX1DUQDguDFjDn16WZhWFcdWFzwdBvS6eqejOlkTNLqPJJvaWand5kBBclFQtVXfxU_qSx7SvCcsJK8XrvRW2nmG2dhjnFV1hW_l52SmtFZQTG7f_A-yR6FsMY4Z1VRPMxOKOd1RRk_zX4vlAIDXkZokYeN1B5Ju3u2o0qhYYyyB6uVjlvkOvTmwwK1ckgxpO0eabZI6V56iBFQGNy3XQqtxkFa1Hhn1UpLg1IXE1D00oYO1K7bTx1X6HKunNGoc36Qg27dZut1urWFm1a92SoXtkYGeJw96KQJ8GS6z7Ivby8_X7yfXV2_W14srmaqqGmc1ayqW1xzQkvSKKqgYEBY1bC2oViBZIyzgrG87UiJVacwLRWpC45zKVuZUmfZ873uxrggJpeDIHVZ8pxTQhKx3BOtk2uxSQNLvxVOanETcL4X0ketDIi8y5uKM1IQChx410haUMpZ2eSqBEqT1vnUbWwGaBXYZJE5Ej3OWL0SvfshWI1rWlVJ4MUk4N33EUL8x8gT1cs0lbadS2Jq0EGJBS-TDCUMJ2r-FyqdFgat0j_rdIofFbw6KkhMhF-xl2MIYvnp4_-z11-P2ZcH7AqkiavgzBi1s-EY5HtQeReCh-7OOYLFbk1u3RC7NRHTmqSyZ4eu3xXd7gX7A0zcD4k</recordid><startdate>20140131</startdate><enddate>20140131</enddate><creator>Foresta, Mara</creator><creator>Izzotti, Alberto</creator><creator>La Maestra, Sebastiano</creator><creator>Micale, Rosanna</creator><creator>Poggi, Alessandro</creator><creator>Vecchio, Donatella</creator><creator>Frosina, Guido</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>AEUYN</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140131</creationdate><title>Accelerated repair and reduced mutagenicity of DNA damage induced by cigarette smoke in human bronchial cells transfected with E.coli formamidopyrimidine DNA glycosylase</title><author>Foresta, Mara ; Izzotti, Alberto ; La Maestra, Sebastiano ; Micale, Rosanna ; Poggi, Alessandro ; Vecchio, Donatella ; Frosina, Guido</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-9389d0941271bc2ce63e138b3db20cea33436335df170cfc027c196405aada363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adducts</topic><topic>Bacteria</topic><topic>Biology</topic><topic>Bronchi - metabolism</topic><topic>Bronchi - pathology</topic><topic>Carcinogens</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cigarette smoke</topic><topic>Cigarettes</topic><topic>Cloning</topic><topic>Condensates</topic><topic>Conditioned stimulus</topic><topic>Damage</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA adducts</topic><topic>DNA Damage</topic><topic>DNA glycosylase</topic><topic>DNA Repair</topic><topic>DNA-Formamidopyrimidine Glycosylase - biosynthesis</topic><topic>DNA-Formamidopyrimidine Glycosylase - genetics</topic><topic>E coli</topic><topic>Enzymes</topic><topic>Escherichia coli - enzymology</topic><topic>Escherichia coli - genetics</topic><topic>Escherichia coli Proteins - biosynthesis</topic><topic>Escherichia coli Proteins - genetics</topic><topic>Female</topic><topic>Fluorescence</topic><topic>Fusion protein</topic><topic>Gene expression</topic><topic>Genetic vectors</topic><topic>Green fluorescent protein</topic><topic>Health sciences</topic><topic>Humans</topic><topic>Ionizing radiation</topic><topic>Kinases</topic><topic>Low concentrations</topic><topic>Lung cancer</topic><topic>Lung carcinoma</topic><topic>Lung diseases</topic><topic>Lungs</topic><topic>Maintenance</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>Mutagenesis</topic><topic>Mutagenicity</topic><topic>Mutation</topic><topic>Na+/K+-exchanging ATPase</topic><topic>Non-small cell lung cancer</topic><topic>Non-small cell lung carcinoma</topic><topic>Oxygen</topic><topic>Polycyclic aromatic hydrocarbons</topic><topic>Proteins</topic><topic>Reactive oxygen species</topic><topic>Recombinant Proteins - 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Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH) inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG) repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP). Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na(+)K(+)-ATPase locus (oua(r)) were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells' capacity to repair damaged DNA.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24498234</pmid><doi>10.1371/journal.pone.0087984</doi><tpages>e87984</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| subjects | Adducts Bacteria Biology Bronchi - metabolism Bronchi - pathology Carcinogens Cell adhesion & migration Cell Line, Tumor Cigarette smoke Cigarettes Cloning Condensates Conditioned stimulus Damage Deoxyribonucleic acid DNA DNA adducts DNA Damage DNA glycosylase DNA Repair DNA-Formamidopyrimidine Glycosylase - biosynthesis DNA-Formamidopyrimidine Glycosylase - genetics E coli Enzymes Escherichia coli - enzymology Escherichia coli - genetics Escherichia coli Proteins - biosynthesis Escherichia coli Proteins - genetics Female Fluorescence Fusion protein Gene expression Genetic vectors Green fluorescent protein Health sciences Humans Ionizing radiation Kinases Low concentrations Lung cancer Lung carcinoma Lung diseases Lungs Maintenance Medical research Medicine Middle Aged Mutagenesis Mutagenicity Mutation Na+/K+-exchanging ATPase Non-small cell lung cancer Non-small cell lung carcinoma Oxygen Polycyclic aromatic hydrocarbons Proteins Reactive oxygen species Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Repair Small cell lung carcinoma Smoke Smoking Tobacco Smoke Pollution - adverse effects Transfection |
| title | Accelerated repair and reduced mutagenicity of DNA damage induced by cigarette smoke in human bronchial cells transfected with E.coli formamidopyrimidine DNA glycosylase |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T01%3A16%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Accelerated%20repair%20and%20reduced%20mutagenicity%20of%20DNA%20damage%20induced%20by%20cigarette%20smoke%20in%20human%20bronchial%20cells%20transfected%20with%20E.coli%20formamidopyrimidine%20DNA%20glycosylase&rft.jtitle=PloS%20one&rft.au=Foresta,%20Mara&rft.date=2014-01-31&rft.volume=9&rft.issue=1&rft.spage=e87984&rft.pages=e87984-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0087984&rft_dat=%3Cgale_plos_%3EA478832130%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1977454211&rft_id=info:pmid/24498234&rft_galeid=A478832130&rft_doaj_id=oai_doaj_org_article_5f5b8431612e4e4fba2622437b5c7e22&rfr_iscdi=true |