The immunomodulating agent gliotoxin causes genomic DNA fragmentation
Gliotoxin, a member of the class of secondary fungal metabolites characterized by the presence of an epipolythiodioxopiperazine ring, caused fragmentation of spleen cell DNA as observed by flow cytometry and gel electrophoresis. Gliotoxin was found to cause substantial double-stranded DNA breakage i...
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| Veröffentlicht in: | Molecular immunology 1987, Vol.24 (1), p.47-55 |
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| container_end_page | 55 |
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| container_issue | 1 |
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| container_title | Molecular immunology |
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| creator | Braithwaite, Antony W. Eichner, Ronald D. Waring, Paul Müllbacher, Arno |
| description | Gliotoxin, a member of the class of secondary fungal metabolites characterized by the presence of an epipolythiodioxopiperazine ring, caused fragmentation of spleen cell DNA as observed by flow cytometry and gel electrophoresis. Gliotoxin was found to cause substantial double-stranded DNA breakage in spleen cells which was dose- and time-dependent. The ability of gliotoxin to cause DNA breakage was also found to be specific to cell type. DNA breakage occurred in all cell types in which gliotoxin inhibited proliferation and so provides a general explanation as to how gliotoxin prevents cell proliferation. Other results showed that gliotoxin bound to a similar extent to both sensitive and resistant cells, indicating that differential uptake is not a likely mechanism to explain cell type selectivity. The results are discussed in terms of a mechanism for gliotoxin action involving genomic DNA as the central target. |
| doi_str_mv | 10.1016/0161-5890(87)90110-6 |
| format | Article |
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Gliotoxin was found to cause substantial double-stranded DNA breakage in spleen cells which was dose- and time-dependent. The ability of gliotoxin to cause DNA breakage was also found to be specific to cell type. DNA breakage occurred in all cell types in which gliotoxin inhibited proliferation and so provides a general explanation as to how gliotoxin prevents cell proliferation. Other results showed that gliotoxin bound to a similar extent to both sensitive and resistant cells, indicating that differential uptake is not a likely mechanism to explain cell type selectivity. The results are discussed in terms of a mechanism for gliotoxin action involving genomic DNA as the central target.</description><identifier>ISSN: 0161-5890</identifier><identifier>EISSN: 1872-9142</identifier><identifier>DOI: 10.1016/0161-5890(87)90110-6</identifier><identifier>PMID: 2441247</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Cell Division - drug effects ; DNA - biosynthesis ; DNA - radiation effects ; DNA Damage ; Dose-Response Relationship, Drug ; Electrophoresis, Agar Gel ; Genes ; Gliotoxin - metabolism ; Gliotoxin - pharmacology ; Immune Tolerance - drug effects ; Lymphocyte Activation - drug effects ; Mice ; Mycotoxins - pharmacology ; Spleen - cytology ; Sporidesmins - pharmacology</subject><ispartof>Molecular immunology, 1987, Vol.24 (1), p.47-55</ispartof><rights>1987</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-348724c29b3e90284eaafa2e3094d16503bd5f8cc31a9c9cfb473a3e819e250e3</citedby><cites>FETCH-LOGICAL-c388t-348724c29b3e90284eaafa2e3094d16503bd5f8cc31a9c9cfb473a3e819e250e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0161589087901106$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2441247$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Braithwaite, Antony W.</creatorcontrib><creatorcontrib>Eichner, Ronald D.</creatorcontrib><creatorcontrib>Waring, Paul</creatorcontrib><creatorcontrib>Müllbacher, Arno</creatorcontrib><title>The immunomodulating agent gliotoxin causes genomic DNA fragmentation</title><title>Molecular immunology</title><addtitle>Mol Immunol</addtitle><description>Gliotoxin, a member of the class of secondary fungal metabolites characterized by the presence of an epipolythiodioxopiperazine ring, caused fragmentation of spleen cell DNA as observed by flow cytometry and gel electrophoresis. Gliotoxin was found to cause substantial double-stranded DNA breakage in spleen cells which was dose- and time-dependent. The ability of gliotoxin to cause DNA breakage was also found to be specific to cell type. DNA breakage occurred in all cell types in which gliotoxin inhibited proliferation and so provides a general explanation as to how gliotoxin prevents cell proliferation. Other results showed that gliotoxin bound to a similar extent to both sensitive and resistant cells, indicating that differential uptake is not a likely mechanism to explain cell type selectivity. The results are discussed in terms of a mechanism for gliotoxin action involving genomic DNA as the central target.</description><subject>Animals</subject><subject>Cell Division - drug effects</subject><subject>DNA - biosynthesis</subject><subject>DNA - radiation effects</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrophoresis, Agar Gel</subject><subject>Genes</subject><subject>Gliotoxin - metabolism</subject><subject>Gliotoxin - pharmacology</subject><subject>Immune Tolerance - drug effects</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Mice</subject><subject>Mycotoxins - pharmacology</subject><subject>Spleen - cytology</subject><subject>Sporidesmins - pharmacology</subject><issn>0161-5890</issn><issn>1872-9142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EKqXwByBlhWAR8CuJvUGqSnlIFWzK2nKcSTFK4mInCP4el1ZdshiNNHPvPA5C5wTfEEzy2xgkzYTEV6K4lpgQnOYHaExEQVNJOD1E473kGJ2E8IExznGejdCIck4oL8ZovnyHxLbt0LnWVUOje9utEr2Crk9WjXW9-7ZdYvQQICSx6lprkvuXaVJ7vWqjKhpcd4qOat0EONvlCXp7mC9nT-ni9fF5Nl2khgnRp4zH27ihsmQgMRUctK41BYYlr0ieYVZWWS2MYURLI01d8oJpBoJIoBkGNkGX27lr7z4HCL1qbTDQNLoDNwRFeCYEJjQK-VZovAvBQ63W3rba_yiC1Yae2qBRGzRKFOqPnsqj7WI3fyhbqPamHa7Yv9v2IT75ZcGrYCx0BirrwfSqcvb_Bb8TIn5Q</recordid><startdate>1987</startdate><enddate>1987</enddate><creator>Braithwaite, Antony W.</creator><creator>Eichner, Ronald D.</creator><creator>Waring, Paul</creator><creator>Müllbacher, Arno</creator><general>Elsevier Ltd</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>7T7</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>1987</creationdate><title>The immunomodulating agent gliotoxin causes genomic DNA fragmentation</title><author>Braithwaite, Antony W. ; Eichner, Ronald D. ; Waring, Paul ; Müllbacher, Arno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-348724c29b3e90284eaafa2e3094d16503bd5f8cc31a9c9cfb473a3e819e250e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Animals</topic><topic>Cell Division - drug effects</topic><topic>DNA - biosynthesis</topic><topic>DNA - radiation effects</topic><topic>DNA Damage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electrophoresis, Agar Gel</topic><topic>Genes</topic><topic>Gliotoxin - metabolism</topic><topic>Gliotoxin - pharmacology</topic><topic>Immune Tolerance - drug effects</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Mice</topic><topic>Mycotoxins - pharmacology</topic><topic>Spleen - cytology</topic><topic>Sporidesmins - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Braithwaite, Antony W.</creatorcontrib><creatorcontrib>Eichner, Ronald D.</creatorcontrib><creatorcontrib>Waring, Paul</creatorcontrib><creatorcontrib>Müllbacher, Arno</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Braithwaite, Antony W.</au><au>Eichner, Ronald D.</au><au>Waring, Paul</au><au>Müllbacher, Arno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The immunomodulating agent gliotoxin causes genomic DNA fragmentation</atitle><jtitle>Molecular immunology</jtitle><addtitle>Mol Immunol</addtitle><date>1987</date><risdate>1987</risdate><volume>24</volume><issue>1</issue><spage>47</spage><epage>55</epage><pages>47-55</pages><issn>0161-5890</issn><eissn>1872-9142</eissn><abstract>Gliotoxin, a member of the class of secondary fungal metabolites characterized by the presence of an epipolythiodioxopiperazine ring, caused fragmentation of spleen cell DNA as observed by flow cytometry and gel electrophoresis. Gliotoxin was found to cause substantial double-stranded DNA breakage in spleen cells which was dose- and time-dependent. The ability of gliotoxin to cause DNA breakage was also found to be specific to cell type. DNA breakage occurred in all cell types in which gliotoxin inhibited proliferation and so provides a general explanation as to how gliotoxin prevents cell proliferation. Other results showed that gliotoxin bound to a similar extent to both sensitive and resistant cells, indicating that differential uptake is not a likely mechanism to explain cell type selectivity. The results are discussed in terms of a mechanism for gliotoxin action involving genomic DNA as the central target.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>2441247</pmid><doi>10.1016/0161-5890(87)90110-6</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0161-5890 |
| ispartof | Molecular immunology, 1987, Vol.24 (1), p.47-55 |
| issn | 0161-5890 1872-9142 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_14588012 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Cell Division - drug effects DNA - biosynthesis DNA - radiation effects DNA Damage Dose-Response Relationship, Drug Electrophoresis, Agar Gel Genes Gliotoxin - metabolism Gliotoxin - pharmacology Immune Tolerance - drug effects Lymphocyte Activation - drug effects Mice Mycotoxins - pharmacology Spleen - cytology Sporidesmins - pharmacology |
| title | The immunomodulating agent gliotoxin causes genomic DNA fragmentation |
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