Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells
Hexavalent chromium is a genotoxic human pulmonary carcinogen that elevates DNA oxidation, apparently through the generation of reactive DNA-damaging intermediates including CrV, CrIV and reactive oxygen species. We tested the hypothesis that elevation of DNA oxidation may also be through inhibition...
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| Veröffentlicht in: | Carcinogenesis (New York) 2002-01, Vol.23 (1), p.55-60 |
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| description | Hexavalent chromium is a genotoxic human pulmonary carcinogen that elevates DNA oxidation, apparently through the generation of reactive DNA-damaging intermediates including CrV, CrIV and reactive oxygen species. We tested the hypothesis that elevation of DNA oxidation may also be through inhibition of the expression of the repair glycosylase for 8-oxo deoxyguanine (hOGG1) in cultured A549 human lung epithelial cells. Treatment with sodium dichromate (0–100 μM, 16 h) resulted in a concentration-dependent decrease in the levels of OGG1 mRNA as measured by both RT–PCR and RNase protection assay. Sodium dichromate at 25 μM and above gave a marked reduction of OGG1 mRNA expression which was not seen at 1 μM and below. No effect on the expression of the apurinic endonuclease hAPE or the house-keeping gene GAPDH was observed at any of the concentrations of sodium dichromate investigated. Treatment of cells with the pro-oxidant H2O2 (0–200 μM) for 16 h had no detectable effect on the levels of OGG1 mRNA or protein expression suggesting that the effect of sodium dichromate is not mediated by H2O2. Western blotting demonstrated that sodium dichromate (100 μM; 16 h and >25 μM; 28 h) markedly reduced levels of OGG1 protein in nuclear cell extracts. Additionally, treatment of cells with sodium dichromate (>25 μM, 28 h) resulted in a concentration-dependent decrease in the ability of nuclear extracts to nick a synthetic oligonucleotide containing 8-oxo deoxyguanine (8-oxo dG). We conclude that the elevation of 8-oxo dG levels observed in A549 cells treated with sodium dichromate may be, at least in part, due to a reduced capacity to repair endogenous and hexavalent chromium-induced 8-oxo dG. |
| doi_str_mv | 10.1093/carcin/23.1.55 |
| format | Article |
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We tested the hypothesis that elevation of DNA oxidation may also be through inhibition of the expression of the repair glycosylase for 8-oxo deoxyguanine (hOGG1) in cultured A549 human lung epithelial cells. Treatment with sodium dichromate (0–100 μM, 16 h) resulted in a concentration-dependent decrease in the levels of OGG1 mRNA as measured by both RT–PCR and RNase protection assay. Sodium dichromate at 25 μM and above gave a marked reduction of OGG1 mRNA expression which was not seen at 1 μM and below. No effect on the expression of the apurinic endonuclease hAPE or the house-keeping gene GAPDH was observed at any of the concentrations of sodium dichromate investigated. Treatment of cells with the pro-oxidant H2O2 (0–200 μM) for 16 h had no detectable effect on the levels of OGG1 mRNA or protein expression suggesting that the effect of sodium dichromate is not mediated by H2O2. Western blotting demonstrated that sodium dichromate (100 μM; 16 h and >25 μM; 28 h) markedly reduced levels of OGG1 protein in nuclear cell extracts. Additionally, treatment of cells with sodium dichromate (>25 μM, 28 h) resulted in a concentration-dependent decrease in the ability of nuclear extracts to nick a synthetic oligonucleotide containing 8-oxo deoxyguanine (8-oxo dG). We conclude that the elevation of 8-oxo dG levels observed in A549 cells treated with sodium dichromate may be, at least in part, due to a reduced capacity to repair endogenous and hexavalent chromium-induced 8-oxo dG.</description><identifier>ISSN: 0143-3334</identifier><identifier>ISSN: 1460-2180</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/23.1.55</identifier><identifier>PMID: 11756223</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>8-oxo 2-deoxyguanine ; 8-oxo dG ; 8-oxoguanine-DNA glycosylase ; Adenosine Triphosphate - metabolism ; Biological and medical sciences ; Blotting, Western ; cAMP-response element-binding protein-binding protein ; Carcinogenesis, carcinogens and anticarcinogens ; CBP ; Cell Extracts ; Chemical agents ; Chromates - pharmacology ; Chromates - toxicity ; CrVI ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - metabolism ; DNA Repair - drug effects ; DNA-Formamidopyrimidine Glycosylase ; Down-Regulation - drug effects ; FaPy ; formamidopyrimidine ; Gene Expression Regulation, Enzymologic - drug effects ; Gene Expression Regulation, Neoplastic - drug effects ; haem oxygenase-1 ; hexavalent chromium ; HO-1 ; hOGG1 protein ; Humans ; Hydrogen Peroxide - pharmacology ; In Situ Nick-End Labeling ; Lung Neoplasms - enzymology ; Medical sciences ; N-Glycosyl Hydrolases - genetics ; N-Glycosyl Hydrolases - metabolism ; NfκB ; Nuclear Proteins - metabolism ; nuclear transcription factor-κB ; reactive oxygen species ; Reactive Oxygen Species - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; ROS ; sodium dichromate ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Carcinogenesis (New York), 2002-01, Vol.23 (1), p.55-60</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Jan 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c523t-b6f5eccacf46907726dda50307b25a6847a3b0303721350ed71e23b478256b1b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13439427$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11756223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hodges, N.J.</creatorcontrib><creatorcontrib>Chipman, J.K.</creatorcontrib><title>Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Hexavalent chromium is a genotoxic human pulmonary carcinogen that elevates DNA oxidation, apparently through the generation of reactive DNA-damaging intermediates including CrV, CrIV and reactive oxygen species. We tested the hypothesis that elevation of DNA oxidation may also be through inhibition of the expression of the repair glycosylase for 8-oxo deoxyguanine (hOGG1) in cultured A549 human lung epithelial cells. Treatment with sodium dichromate (0–100 μM, 16 h) resulted in a concentration-dependent decrease in the levels of OGG1 mRNA as measured by both RT–PCR and RNase protection assay. Sodium dichromate at 25 μM and above gave a marked reduction of OGG1 mRNA expression which was not seen at 1 μM and below. No effect on the expression of the apurinic endonuclease hAPE or the house-keeping gene GAPDH was observed at any of the concentrations of sodium dichromate investigated. Treatment of cells with the pro-oxidant H2O2 (0–200 μM) for 16 h had no detectable effect on the levels of OGG1 mRNA or protein expression suggesting that the effect of sodium dichromate is not mediated by H2O2. Western blotting demonstrated that sodium dichromate (100 μM; 16 h and >25 μM; 28 h) markedly reduced levels of OGG1 protein in nuclear cell extracts. Additionally, treatment of cells with sodium dichromate (>25 μM, 28 h) resulted in a concentration-dependent decrease in the ability of nuclear extracts to nick a synthetic oligonucleotide containing 8-oxo deoxyguanine (8-oxo dG). We conclude that the elevation of 8-oxo dG levels observed in A549 cells treated with sodium dichromate may be, at least in part, due to a reduced capacity to repair endogenous and hexavalent chromium-induced 8-oxo dG.</description><subject>8-oxo 2-deoxyguanine</subject><subject>8-oxo dG</subject><subject>8-oxoguanine-DNA glycosylase</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>cAMP-response element-binding protein-binding protein</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>CBP</subject><subject>Cell Extracts</subject><subject>Chemical agents</subject><subject>Chromates - pharmacology</subject><subject>Chromates - toxicity</subject><subject>CrVI</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - metabolism</subject><subject>DNA Repair - drug effects</subject><subject>DNA-Formamidopyrimidine Glycosylase</subject><subject>Down-Regulation - drug effects</subject><subject>FaPy</subject><subject>formamidopyrimidine</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>haem oxygenase-1</subject><subject>hexavalent chromium</subject><subject>HO-1</subject><subject>hOGG1 protein</subject><subject>Humans</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>In Situ Nick-End Labeling</subject><subject>Lung Neoplasms - enzymology</subject><subject>Medical sciences</subject><subject>N-Glycosyl Hydrolases - genetics</subject><subject>N-Glycosyl Hydrolases - metabolism</subject><subject>NfκB</subject><subject>Nuclear Proteins - metabolism</subject><subject>nuclear transcription factor-κB</subject><subject>reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>ROS</subject><subject>sodium dichromate</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0143-3334</issn><issn>1460-2180</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0c9vFCEUB3BiNHatXj0aYqLRw2yBNww7x7XVrUljTVN_xAthGGaXdgZWGGL3L_HflXU2NvFE4H2A78tD6Dklc0pqONEqaOtOGMzpnPMHaEbLihSMLshDNCO0hAIAyiP0JMYbQmgFvH6MjigVvGIMZuj3mf_limDWqVej9Q77Do8bg88-LfPpVtmAjWu9S7o3Khq8KPydL9ZJOev-Krzud9rHXb-vUvxmc7la0be42eHoW5sG3Fq9CX5Qo8HWYZ36MQXT4k0alMNLXta4T26Np0ayw9r0fXyKHnWqj-bZYT1GXz68vz49Ly4uVx9PlxeF5gzGoqk6brRWuiurmgjBqrZVnAARDeOqWpRCQZO3IBgFTkwrqGHQlGLBeNXQBo7R6-ndbfA_k4mjHGzcJ1DO-BQlXQAwUYkMX_4Hb3wKLmeTjNbAM2EZzSekg48xmE5ugx1U2ElK5H5ecmpTMpBUcp4vvDi8mprBtPf8MKAMXh2Ailr1XVBO23jvoIS6ZPt4xeRsHM3dv7oKtzInE1yef_8hrz9fvbuqvn3N3_8Bn2atEQ</recordid><startdate>200201</startdate><enddate>200201</enddate><creator>Hodges, N.J.</creator><creator>Chipman, J.K.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>200201</creationdate><title>Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells</title><author>Hodges, N.J. ; Chipman, J.K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c523t-b6f5eccacf46907726dda50307b25a6847a3b0303721350ed71e23b478256b1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>8-oxo 2-deoxyguanine</topic><topic>8-oxo dG</topic><topic>8-oxoguanine-DNA glycosylase</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>cAMP-response element-binding protein-binding protein</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>CBP</topic><topic>Cell Extracts</topic><topic>Chemical agents</topic><topic>Chromates - pharmacology</topic><topic>Chromates - toxicity</topic><topic>CrVI</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - metabolism</topic><topic>DNA Repair - drug effects</topic><topic>DNA-Formamidopyrimidine Glycosylase</topic><topic>Down-Regulation - drug effects</topic><topic>FaPy</topic><topic>formamidopyrimidine</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>haem oxygenase-1</topic><topic>hexavalent chromium</topic><topic>HO-1</topic><topic>hOGG1 protein</topic><topic>Humans</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>In Situ Nick-End Labeling</topic><topic>Lung Neoplasms - enzymology</topic><topic>Medical sciences</topic><topic>N-Glycosyl Hydrolases - genetics</topic><topic>N-Glycosyl Hydrolases - metabolism</topic><topic>NfκB</topic><topic>Nuclear Proteins - metabolism</topic><topic>nuclear transcription factor-κB</topic><topic>reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>ROS</topic><topic>sodium dichromate</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hodges, N.J.</creatorcontrib><creatorcontrib>Chipman, J.K.</creatorcontrib><collection>Istex</collection><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>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hodges, N.J.</au><au>Chipman, J.K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2002-01</date><risdate>2002</risdate><volume>23</volume><issue>1</issue><spage>55</spage><epage>60</epage><pages>55-60</pages><issn>0143-3334</issn><issn>1460-2180</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>Hexavalent chromium is a genotoxic human pulmonary carcinogen that elevates DNA oxidation, apparently through the generation of reactive DNA-damaging intermediates including CrV, CrIV and reactive oxygen species. We tested the hypothesis that elevation of DNA oxidation may also be through inhibition of the expression of the repair glycosylase for 8-oxo deoxyguanine (hOGG1) in cultured A549 human lung epithelial cells. Treatment with sodium dichromate (0–100 μM, 16 h) resulted in a concentration-dependent decrease in the levels of OGG1 mRNA as measured by both RT–PCR and RNase protection assay. Sodium dichromate at 25 μM and above gave a marked reduction of OGG1 mRNA expression which was not seen at 1 μM and below. No effect on the expression of the apurinic endonuclease hAPE or the house-keeping gene GAPDH was observed at any of the concentrations of sodium dichromate investigated. Treatment of cells with the pro-oxidant H2O2 (0–200 μM) for 16 h had no detectable effect on the levels of OGG1 mRNA or protein expression suggesting that the effect of sodium dichromate is not mediated by H2O2. Western blotting demonstrated that sodium dichromate (100 μM; 16 h and >25 μM; 28 h) markedly reduced levels of OGG1 protein in nuclear cell extracts. Additionally, treatment of cells with sodium dichromate (>25 μM, 28 h) resulted in a concentration-dependent decrease in the ability of nuclear extracts to nick a synthetic oligonucleotide containing 8-oxo deoxyguanine (8-oxo dG). We conclude that the elevation of 8-oxo dG levels observed in A549 cells treated with sodium dichromate may be, at least in part, due to a reduced capacity to repair endogenous and hexavalent chromium-induced 8-oxo dG.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>11756223</pmid><doi>10.1093/carcin/23.1.55</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | 8-oxo 2-deoxyguanine 8-oxo dG 8-oxoguanine-DNA glycosylase Adenosine Triphosphate - metabolism Biological and medical sciences Blotting, Western cAMP-response element-binding protein-binding protein Carcinogenesis, carcinogens and anticarcinogens CBP Cell Extracts Chemical agents Chromates - pharmacology Chromates - toxicity CrVI Deoxyguanosine - analogs & derivatives Deoxyguanosine - metabolism DNA Repair - drug effects DNA-Formamidopyrimidine Glycosylase Down-Regulation - drug effects FaPy formamidopyrimidine Gene Expression Regulation, Enzymologic - drug effects Gene Expression Regulation, Neoplastic - drug effects haem oxygenase-1 hexavalent chromium HO-1 hOGG1 protein Humans Hydrogen Peroxide - pharmacology In Situ Nick-End Labeling Lung Neoplasms - enzymology Medical sciences N-Glycosyl Hydrolases - genetics N-Glycosyl Hydrolases - metabolism NfκB Nuclear Proteins - metabolism nuclear transcription factor-κB reactive oxygen species Reactive Oxygen Species - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism ROS sodium dichromate Tumor Cells, Cultured Tumors |
| title | Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells |
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