DNA damage by nitrogen mustard in a gene containing multiple Sp1-binding sites
The human cytochrome c 1 gene TATA-less promoter contains 10 Sp1-binding elements that regulate the activation of transcription of this gene. Quantitative PCR was used to show that nitrogen mustard induces DNA lesions within this Sp1-binding region following exposure of HeLa cells to clinical levels...
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| Veröffentlicht in: | Mutation research 1999-09, Vol.445 (1), p.45-54 |
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| container_title | Mutation research |
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| creator | Chen, Xin-Ming Cullinane, Carleen Gray, Peter J Phillips, Don R |
| description | The human cytochrome
c
1 gene TATA-less promoter contains 10 Sp1-binding elements that regulate the activation of transcription of this gene. Quantitative PCR was used to show that nitrogen mustard induces DNA lesions within this Sp1-binding region following exposure of HeLa cells to clinical levels of the drug. Alkylation of the cytochrome
c
1 gene in HeLa cells increased with reaction time up to 4 h following exposure to nitrogen mustard, with 50% of the lesions (approximately 0.8/kb) forming within 1 h. An Sp1 competition assay showed that nitrogen mustard inhibited the binding of Sp1 to the promoter region of the cytochrome
c
1 gene in HeLa cells. These results show that nitrogen mustard-induced damage to Sp1-binding sites may contribute to the toxicity of this compound by interfering with the activation of specific genes. |
| doi_str_mv | 10.1016/S1383-5718(99)00114-X |
| format | Article |
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c
1 gene TATA-less promoter contains 10 Sp1-binding elements that regulate the activation of transcription of this gene. Quantitative PCR was used to show that nitrogen mustard induces DNA lesions within this Sp1-binding region following exposure of HeLa cells to clinical levels of the drug. Alkylation of the cytochrome
c
1 gene in HeLa cells increased with reaction time up to 4 h following exposure to nitrogen mustard, with 50% of the lesions (approximately 0.8/kb) forming within 1 h. An Sp1 competition assay showed that nitrogen mustard inhibited the binding of Sp1 to the promoter region of the cytochrome
c
1 gene in HeLa cells. These results show that nitrogen mustard-induced damage to Sp1-binding sites may contribute to the toxicity of this compound by interfering with the activation of specific genes.</description><identifier>ISSN: 1383-5718</identifier><identifier>ISSN: 0027-5107</identifier><identifier>EISSN: 1879-3592</identifier><identifier>DOI: 10.1016/S1383-5718(99)00114-X</identifier><identifier>PMID: 10521690</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Alkylating agent ; Alkylating Agents - toxicity ; Alkylation - drug effects ; Base Sequence ; Binding Sites - genetics ; Binding, Competitive ; Biological and medical sciences ; cytochrome c ; Cytochrome c1 gene ; Cytochromes c1 - genetics ; DNA Damage ; DNA, Neoplasm - drug effects ; DNA, Neoplasm - genetics ; DNA, Neoplasm - metabolism ; Dose-Response Relationship, Drug ; Drug toxicity and drugs side effects treatment ; HeLa Cells ; Humans ; mechlorethamine ; Mechlorethamine - toxicity ; Medical sciences ; Miscellaneous (drug allergy, mutagens, teratogens...) ; Molecular Sequence Data ; nitrogen mustards ; Pharmacology. Drug treatments ; Promoter Regions, Genetic - genetics ; Quantitative PCR ; Sp1 ; Sp1 protein ; Sp1 Transcription Factor - metabolism ; Tetrahydrofolate Dehydrogenase - genetics</subject><ispartof>Mutation research, 1999-09, Vol.445 (1), p.45-54</ispartof><rights>1999 Elsevier Science B.V.</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-8003c8b77b8a22023cc9a8c1b4b3e4f9b98cc43982a2d9802bb31f952c9a26f43</citedby><cites>FETCH-LOGICAL-c452t-8003c8b77b8a22023cc9a8c1b4b3e4f9b98cc43982a2d9802bb31f952c9a26f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S1383-5718(99)00114-X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1952139$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10521690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xin-Ming</creatorcontrib><creatorcontrib>Cullinane, Carleen</creatorcontrib><creatorcontrib>Gray, Peter J</creatorcontrib><creatorcontrib>Phillips, Don R</creatorcontrib><title>DNA damage by nitrogen mustard in a gene containing multiple Sp1-binding sites</title><title>Mutation research</title><addtitle>Mutat Res</addtitle><description>The human cytochrome
c
1 gene TATA-less promoter contains 10 Sp1-binding elements that regulate the activation of transcription of this gene. Quantitative PCR was used to show that nitrogen mustard induces DNA lesions within this Sp1-binding region following exposure of HeLa cells to clinical levels of the drug. Alkylation of the cytochrome
c
1 gene in HeLa cells increased with reaction time up to 4 h following exposure to nitrogen mustard, with 50% of the lesions (approximately 0.8/kb) forming within 1 h. An Sp1 competition assay showed that nitrogen mustard inhibited the binding of Sp1 to the promoter region of the cytochrome
c
1 gene in HeLa cells. These results show that nitrogen mustard-induced damage to Sp1-binding sites may contribute to the toxicity of this compound by interfering with the activation of specific genes.</description><subject>Alkylating agent</subject><subject>Alkylating Agents - toxicity</subject><subject>Alkylation - drug effects</subject><subject>Base Sequence</subject><subject>Binding Sites - genetics</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>cytochrome c</subject><subject>Cytochrome c1 gene</subject><subject>Cytochromes c1 - genetics</subject><subject>DNA Damage</subject><subject>DNA, Neoplasm - drug effects</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>mechlorethamine</subject><subject>Mechlorethamine - toxicity</subject><subject>Medical sciences</subject><subject>Miscellaneous (drug allergy, mutagens, teratogens...)</subject><subject>Molecular Sequence Data</subject><subject>nitrogen mustards</subject><subject>Pharmacology. Drug treatments</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Quantitative PCR</subject><subject>Sp1</subject><subject>Sp1 protein</subject><subject>Sp1 Transcription Factor - metabolism</subject><subject>Tetrahydrofolate Dehydrogenase - genetics</subject><issn>1383-5718</issn><issn>0027-5107</issn><issn>1879-3592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtKAzEUhoMo3h9ByUJEF6O5zHSSlZR6BamLKrgLSeZMicxkajIV-vamtqI7XSWcfP85Jx9CR5RcUEIHlxPKBc-KkoozKc8JoTTPXjfQLhWlzHgh2Wa6fyM7aC_GN0IY4URsox1KCkYHkuyi8fV4iCvd6ilgs8De9aGbgsftPPY6VNh5rHEqALad77Xzzk_TY9O7WQN4MqOZcb5aFqPrIR6grVo3EQ7X5z56ub15Ht1nj093D6PhY2bzgvWZIIRbYcrSCM0YYdxaqYWlJjcc8loaKazNuRRMs0oKwozhtJYFSxgb1DnfR6ervrPQvc8h9qp10ULTaA_dPCpacjngpPwPmEwUy47FCrShizFArWbBtTosFCVqaVx9GVdLnUpK9WVcvabc8XrA3LRQ_UqtFCfgZA3oaHVTB-2tiz9c-hXlMmFXKwyStg8HQUXrwFuoXADbq6pzf2zyCc62m9w</recordid><startdate>19990915</startdate><enddate>19990915</enddate><creator>Chen, Xin-Ming</creator><creator>Cullinane, Carleen</creator><creator>Gray, Peter J</creator><creator>Phillips, Don R</creator><general>Elsevier B.V</general><general>Elsevier</general><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>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19990915</creationdate><title>DNA damage by nitrogen mustard in a gene containing multiple Sp1-binding sites</title><author>Chen, Xin-Ming ; Cullinane, Carleen ; Gray, Peter J ; Phillips, Don R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-8003c8b77b8a22023cc9a8c1b4b3e4f9b98cc43982a2d9802bb31f952c9a26f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Alkylating agent</topic><topic>Alkylating Agents - toxicity</topic><topic>Alkylation - drug effects</topic><topic>Base Sequence</topic><topic>Binding Sites - genetics</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>cytochrome c</topic><topic>Cytochrome c1 gene</topic><topic>Cytochromes c1 - genetics</topic><topic>DNA Damage</topic><topic>DNA, Neoplasm - drug effects</topic><topic>DNA, Neoplasm - genetics</topic><topic>DNA, Neoplasm - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>mechlorethamine</topic><topic>Mechlorethamine - toxicity</topic><topic>Medical sciences</topic><topic>Miscellaneous (drug allergy, mutagens, teratogens...)</topic><topic>Molecular Sequence Data</topic><topic>nitrogen mustards</topic><topic>Pharmacology. Drug treatments</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Quantitative PCR</topic><topic>Sp1</topic><topic>Sp1 protein</topic><topic>Sp1 Transcription Factor - metabolism</topic><topic>Tetrahydrofolate Dehydrogenase - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xin-Ming</creatorcontrib><creatorcontrib>Cullinane, Carleen</creatorcontrib><creatorcontrib>Gray, Peter J</creatorcontrib><creatorcontrib>Phillips, Don R</creatorcontrib><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>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Mutation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xin-Ming</au><au>Cullinane, Carleen</au><au>Gray, Peter J</au><au>Phillips, Don R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA damage by nitrogen mustard in a gene containing multiple Sp1-binding sites</atitle><jtitle>Mutation research</jtitle><addtitle>Mutat Res</addtitle><date>1999-09-15</date><risdate>1999</risdate><volume>445</volume><issue>1</issue><spage>45</spage><epage>54</epage><pages>45-54</pages><issn>1383-5718</issn><issn>0027-5107</issn><eissn>1879-3592</eissn><abstract>The human cytochrome
c
1 gene TATA-less promoter contains 10 Sp1-binding elements that regulate the activation of transcription of this gene. Quantitative PCR was used to show that nitrogen mustard induces DNA lesions within this Sp1-binding region following exposure of HeLa cells to clinical levels of the drug. Alkylation of the cytochrome
c
1 gene in HeLa cells increased with reaction time up to 4 h following exposure to nitrogen mustard, with 50% of the lesions (approximately 0.8/kb) forming within 1 h. An Sp1 competition assay showed that nitrogen mustard inhibited the binding of Sp1 to the promoter region of the cytochrome
c
1 gene in HeLa cells. These results show that nitrogen mustard-induced damage to Sp1-binding sites may contribute to the toxicity of this compound by interfering with the activation of specific genes.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>10521690</pmid><doi>10.1016/S1383-5718(99)00114-X</doi><tpages>10</tpages></addata></record> |
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| ispartof | Mutation research, 1999-09, Vol.445 (1), p.45-54 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Alkylating agent Alkylating Agents - toxicity Alkylation - drug effects Base Sequence Binding Sites - genetics Binding, Competitive Biological and medical sciences cytochrome c Cytochrome c1 gene Cytochromes c1 - genetics DNA Damage DNA, Neoplasm - drug effects DNA, Neoplasm - genetics DNA, Neoplasm - metabolism Dose-Response Relationship, Drug Drug toxicity and drugs side effects treatment HeLa Cells Humans mechlorethamine Mechlorethamine - toxicity Medical sciences Miscellaneous (drug allergy, mutagens, teratogens...) Molecular Sequence Data nitrogen mustards Pharmacology. Drug treatments Promoter Regions, Genetic - genetics Quantitative PCR Sp1 Sp1 protein Sp1 Transcription Factor - metabolism Tetrahydrofolate Dehydrogenase - genetics |
| title | DNA damage by nitrogen mustard in a gene containing multiple Sp1-binding sites |
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