The effect of DNA-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line
A model system was developed to investigate the effects of DNA alkylating agents on cellular gene expression. The cytomegalovirus immediate-early promoter (CMV) and the mouse mammary tumor virus promoter (MMTV) were coupled separately to the luciferase reporter gene and stably expressed in cultured...
Gespeichert in:
| Veröffentlicht in: | Anti-cancer drugs 2002-03, Vol.13 (3), p.271-280 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 280 |
|---|---|
| container_issue | 3 |
| container_start_page | 271 |
| container_title | Anti-cancer drugs |
| container_volume | 13 |
| creator | Gieseg, Michael A de Bock, Charley Turner, Pamela Ferguson, Lynette R Denny, William A |
| description | A model system was developed to investigate the effects of DNA alkylating agents on cellular gene expression. The cytomegalovirus immediate-early promoter (CMV) and the mouse mammary tumor virus promoter (MMTV) were coupled separately to the luciferase reporter gene and stably expressed in cultured cells. The change in luciferase activity was used as a measure of gene expression inhibition. Seven well-characterized DNA alkylating agents of varied DNA adduct-forming ability were evaluated in this system. The major groove binders/intercalators (that form guanine adducts) increased CMV–luciferase activity above background, while minor groove binders (that form adenine adducts) all decreased it. The MMTV–luciferase activity was remarkably different to the CMV–luciferase activity and was inhibited to the greatest extent by the minor groove alkylators. One of these, a polybenzamide with spatially separated alkylating groups, inhibited gene expression to a greater extent than inhibition of general DNA or RNA synthesis. |
| doi_str_mv | 10.1097/00001813-200203000-00009 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1097_00001813_200203000_00009</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>11984071</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3569-e461ad1aa9ba5d88c32e5d988e62c6fcdb680a00a92a0f62abd3fedaa1f6a3a93</originalsourceid><addsrcrecordid>eNp1kctOwzAQRS0EoqXwC8g_ELDjvLysylOqYFPW0SQZt6FJHNmuQv8epy2wwpvxXJ9rea4JoZzdcSbTe-YXz7gIQsZCJnwXjJI8I1MepSKI04ifkymTsQwimYoJubL20xNeF5dkwrnMIpbyKRlWG6SoFJaOakUf3uYBNNt9A67u1hTW2DlLdUf9xnNfvUFra98ro1vqBk3rzuHagMOKGuy1cWgOsPUnFGirdxZpC20LZk_drtWGNnWH1-RCQWPx5lRn5OPpcbV4CZbvz6-L-TIoRZzIAKOEQ8UBZAFxlWWlCDGuZJZhEpaJKqsiyRgwBjIEppIQikoorAC4SkCAFDOSHe8tjbbWoMp7U49vyTnLxyzznyzz3ywP0mi9PVr7XdFi9Wc8heeB6AgMuvFj222zG9DkG4TGbfL__kh8A_q7gVg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>The effect of DNA-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Gieseg, Michael A ; de Bock, Charley ; Turner, Pamela ; Ferguson, Lynette R ; Denny, William A</creator><creatorcontrib>Gieseg, Michael A ; de Bock, Charley ; Turner, Pamela ; Ferguson, Lynette R ; Denny, William A</creatorcontrib><description>A model system was developed to investigate the effects of DNA alkylating agents on cellular gene expression. The cytomegalovirus immediate-early promoter (CMV) and the mouse mammary tumor virus promoter (MMTV) were coupled separately to the luciferase reporter gene and stably expressed in cultured cells. The change in luciferase activity was used as a measure of gene expression inhibition. Seven well-characterized DNA alkylating agents of varied DNA adduct-forming ability were evaluated in this system. The major groove binders/intercalators (that form guanine adducts) increased CMV–luciferase activity above background, while minor groove binders (that form adenine adducts) all decreased it. The MMTV–luciferase activity was remarkably different to the CMV–luciferase activity and was inhibited to the greatest extent by the minor groove alkylators. One of these, a polybenzamide with spatially separated alkylating groups, inhibited gene expression to a greater extent than inhibition of general DNA or RNA synthesis.</description><identifier>ISSN: 0959-4973</identifier><identifier>EISSN: 1473-5741</identifier><identifier>DOI: 10.1097/00001813-200203000-00009</identifier><identifier>PMID: 11984071</identifier><language>eng</language><publisher>England: Lippincott Williams & Wilkins, Inc</publisher><subject>Alkylating Agents - pharmacology ; Animals ; Cytomegalovirus - genetics ; DNA Adducts - drug effects ; DNA, Neoplasm - drug effects ; Dose-Response Relationship, Drug ; Gene Expression - drug effects ; Genetic Vectors ; Humans ; Luciferases - genetics ; Luciferases - metabolism ; Mammary Neoplasms, Experimental - genetics ; Mammary Neoplasms, Experimental - metabolism ; Mammary Tumor Virus, Mouse - genetics ; Mice ; RNA - antagonists & inhibitors ; RNA - metabolism ; Thymidine - metabolism ; Transfection</subject><ispartof>Anti-cancer drugs, 2002-03, Vol.13 (3), p.271-280</ispartof><rights>2002 Lippincott Williams & Wilkins, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3569-e461ad1aa9ba5d88c32e5d988e62c6fcdb680a00a92a0f62abd3fedaa1f6a3a93</citedby><cites>FETCH-LOGICAL-c3569-e461ad1aa9ba5d88c32e5d988e62c6fcdb680a00a92a0f62abd3fedaa1f6a3a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11984071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gieseg, Michael A</creatorcontrib><creatorcontrib>de Bock, Charley</creatorcontrib><creatorcontrib>Turner, Pamela</creatorcontrib><creatorcontrib>Ferguson, Lynette R</creatorcontrib><creatorcontrib>Denny, William A</creatorcontrib><title>The effect of DNA-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line</title><title>Anti-cancer drugs</title><addtitle>Anticancer Drugs</addtitle><description>A model system was developed to investigate the effects of DNA alkylating agents on cellular gene expression. The cytomegalovirus immediate-early promoter (CMV) and the mouse mammary tumor virus promoter (MMTV) were coupled separately to the luciferase reporter gene and stably expressed in cultured cells. The change in luciferase activity was used as a measure of gene expression inhibition. Seven well-characterized DNA alkylating agents of varied DNA adduct-forming ability were evaluated in this system. The major groove binders/intercalators (that form guanine adducts) increased CMV–luciferase activity above background, while minor groove binders (that form adenine adducts) all decreased it. The MMTV–luciferase activity was remarkably different to the CMV–luciferase activity and was inhibited to the greatest extent by the minor groove alkylators. One of these, a polybenzamide with spatially separated alkylating groups, inhibited gene expression to a greater extent than inhibition of general DNA or RNA synthesis.</description><subject>Alkylating Agents - pharmacology</subject><subject>Animals</subject><subject>Cytomegalovirus - genetics</subject><subject>DNA Adducts - drug effects</subject><subject>DNA, Neoplasm - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Gene Expression - drug effects</subject><subject>Genetic Vectors</subject><subject>Humans</subject><subject>Luciferases - genetics</subject><subject>Luciferases - metabolism</subject><subject>Mammary Neoplasms, Experimental - genetics</subject><subject>Mammary Neoplasms, Experimental - metabolism</subject><subject>Mammary Tumor Virus, Mouse - genetics</subject><subject>Mice</subject><subject>RNA - antagonists & inhibitors</subject><subject>RNA - metabolism</subject><subject>Thymidine - metabolism</subject><subject>Transfection</subject><issn>0959-4973</issn><issn>1473-5741</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctOwzAQRS0EoqXwC8g_ELDjvLysylOqYFPW0SQZt6FJHNmuQv8epy2wwpvxXJ9rea4JoZzdcSbTe-YXz7gIQsZCJnwXjJI8I1MepSKI04ifkymTsQwimYoJubL20xNeF5dkwrnMIpbyKRlWG6SoFJaOakUf3uYBNNt9A67u1hTW2DlLdUf9xnNfvUFra98ro1vqBk3rzuHagMOKGuy1cWgOsPUnFGirdxZpC20LZk_drtWGNnWH1-RCQWPx5lRn5OPpcbV4CZbvz6-L-TIoRZzIAKOEQ8UBZAFxlWWlCDGuZJZhEpaJKqsiyRgwBjIEppIQikoorAC4SkCAFDOSHe8tjbbWoMp7U49vyTnLxyzznyzz3ywP0mi9PVr7XdFi9Wc8heeB6AgMuvFj222zG9DkG4TGbfL__kh8A_q7gVg</recordid><startdate>200203</startdate><enddate>200203</enddate><creator>Gieseg, Michael A</creator><creator>de Bock, Charley</creator><creator>Turner, Pamela</creator><creator>Ferguson, Lynette R</creator><creator>Denny, William A</creator><general>Lippincott Williams & Wilkins, Inc</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></search><sort><creationdate>200203</creationdate><title>The effect of DNA-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line</title><author>Gieseg, Michael A ; de Bock, Charley ; Turner, Pamela ; Ferguson, Lynette R ; Denny, William A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3569-e461ad1aa9ba5d88c32e5d988e62c6fcdb680a00a92a0f62abd3fedaa1f6a3a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Alkylating Agents - pharmacology</topic><topic>Animals</topic><topic>Cytomegalovirus - genetics</topic><topic>DNA Adducts - drug effects</topic><topic>DNA, Neoplasm - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Gene Expression - drug effects</topic><topic>Genetic Vectors</topic><topic>Humans</topic><topic>Luciferases - genetics</topic><topic>Luciferases - metabolism</topic><topic>Mammary Neoplasms, Experimental - genetics</topic><topic>Mammary Neoplasms, Experimental - metabolism</topic><topic>Mammary Tumor Virus, Mouse - genetics</topic><topic>Mice</topic><topic>RNA - antagonists & inhibitors</topic><topic>RNA - metabolism</topic><topic>Thymidine - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gieseg, Michael A</creatorcontrib><creatorcontrib>de Bock, Charley</creatorcontrib><creatorcontrib>Turner, Pamela</creatorcontrib><creatorcontrib>Ferguson, Lynette R</creatorcontrib><creatorcontrib>Denny, William A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Anti-cancer drugs</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gieseg, Michael A</au><au>de Bock, Charley</au><au>Turner, Pamela</au><au>Ferguson, Lynette R</au><au>Denny, William A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of DNA-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line</atitle><jtitle>Anti-cancer drugs</jtitle><addtitle>Anticancer Drugs</addtitle><date>2002-03</date><risdate>2002</risdate><volume>13</volume><issue>3</issue><spage>271</spage><epage>280</epage><pages>271-280</pages><issn>0959-4973</issn><eissn>1473-5741</eissn><abstract>A model system was developed to investigate the effects of DNA alkylating agents on cellular gene expression. The cytomegalovirus immediate-early promoter (CMV) and the mouse mammary tumor virus promoter (MMTV) were coupled separately to the luciferase reporter gene and stably expressed in cultured cells. The change in luciferase activity was used as a measure of gene expression inhibition. Seven well-characterized DNA alkylating agents of varied DNA adduct-forming ability were evaluated in this system. The major groove binders/intercalators (that form guanine adducts) increased CMV–luciferase activity above background, while minor groove binders (that form adenine adducts) all decreased it. The MMTV–luciferase activity was remarkably different to the CMV–luciferase activity and was inhibited to the greatest extent by the minor groove alkylators. One of these, a polybenzamide with spatially separated alkylating groups, inhibited gene expression to a greater extent than inhibition of general DNA or RNA synthesis.</abstract><cop>England</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>11984071</pmid><doi>10.1097/00001813-200203000-00009</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0959-4973 |
| ispartof | Anti-cancer drugs, 2002-03, Vol.13 (3), p.271-280 |
| issn | 0959-4973 1473-5741 |
| language | eng |
| recordid | cdi_crossref_primary_10_1097_00001813_200203000_00009 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | Alkylating Agents - pharmacology Animals Cytomegalovirus - genetics DNA Adducts - drug effects DNA, Neoplasm - drug effects Dose-Response Relationship, Drug Gene Expression - drug effects Genetic Vectors Humans Luciferases - genetics Luciferases - metabolism Mammary Neoplasms, Experimental - genetics Mammary Neoplasms, Experimental - metabolism Mammary Tumor Virus, Mouse - genetics Mice RNA - antagonists & inhibitors RNA - metabolism Thymidine - metabolism Transfection |
| title | The effect of DNA-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T13%3A39%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20effect%20of%20DNA-alkylating%20agents%20on%20gene%20expression%20from%20two%20integrated%20reporter%20genes%20in%20a%20mouse%20mammary%20tumor%20line&rft.jtitle=Anti-cancer%20drugs&rft.au=Gieseg,%20Michael%20A&rft.date=2002-03&rft.volume=13&rft.issue=3&rft.spage=271&rft.epage=280&rft.pages=271-280&rft.issn=0959-4973&rft.eissn=1473-5741&rft_id=info:doi/10.1097/00001813-200203000-00009&rft_dat=%3Cpubmed_cross%3E11984071%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/11984071&rfr_iscdi=true |