In vitro genotoxicity of danthron and its potential mechanism
To ascertain the in vitro genotoxicity of danthron and its potential mechanism of action, we performed an Ames test, a cytokinesis-block micronucleus assay and a comet assay in Balb/c 3T3 cells. The Ames test revealed that danthron was mutagenic only toward Salmonella typhimurium strain TA102 in the...
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description | To ascertain the in vitro genotoxicity of danthron and its potential mechanism of action, we performed an Ames test, a cytokinesis-block micronucleus assay and a comet assay in Balb/c 3T3 cells. The Ames test revealed that danthron was mutagenic only toward Salmonella typhimurium strain TA102 in the presence of an exogenous metabolic activation system (S9 mix). Danthron (25, 50 and 100μg/ml) increased the frequencies of micronuclear cells with or without S9 mix, and the comet length, tail length and Olive tail moment in comet assays without S9 mix in a dose-dependent manner. These results demonstrated the in vitro genotoxicity of danthron and that 3T3 cells are capable of activating danthron. When NADP was replaced by NAD in the S9 mix, danthron remained mutagenic toward strain TA102. The addition of dicoumarol, a DT-diaphorase inhibitor, decreased the number of danthron-induced histidine revertants by 35–39%, indicating that DT-diaphorase is involved in the metabolic activation of danthron in the presence of NADH as an electron donor. In 3T3 cells, increases in reactive oxygen species (ROS) formation and 8-hydroxydeoxyguanosine levels as well as a reduction in GSH levels were induced by danthron in a dose-dependent manner, indicating that oxidative stress may be a major contributing pathway in the genotoxicity of danthron. |
doi_str_mv | 10.1016/j.mrgentox.2011.02.006 |
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The Ames test revealed that danthron was mutagenic only toward Salmonella typhimurium strain TA102 in the presence of an exogenous metabolic activation system (S9 mix). Danthron (25, 50 and 100μg/ml) increased the frequencies of micronuclear cells with or without S9 mix, and the comet length, tail length and Olive tail moment in comet assays without S9 mix in a dose-dependent manner. These results demonstrated the in vitro genotoxicity of danthron and that 3T3 cells are capable of activating danthron. When NADP was replaced by NAD in the S9 mix, danthron remained mutagenic toward strain TA102. The addition of dicoumarol, a DT-diaphorase inhibitor, decreased the number of danthron-induced histidine revertants by 35–39%, indicating that DT-diaphorase is involved in the metabolic activation of danthron in the presence of NADH as an electron donor. In 3T3 cells, increases in reactive oxygen species (ROS) formation and 8-hydroxydeoxyguanosine levels as well as a reduction in GSH levels were induced by danthron in a dose-dependent manner, indicating that oxidative stress may be a major contributing pathway in the genotoxicity of danthron.</description><identifier>ISSN: 1383-5718</identifier><identifier>ISSN: 0027-5107</identifier><identifier>EISSN: 1879-3592</identifier><identifier>DOI: 10.1016/j.mrgentox.2011.02.006</identifier><identifier>PMID: 21354327</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>1,8-Dihydroxyanthraquinone ; Animals ; Anthraquinones - metabolism ; Anthraquinones - toxicity ; BALB 3T3 Cells ; Bioassays ; Biological and medical sciences ; Biotransformation ; Comet Assay ; Cytokines ; Danthron ; Dicumarol - pharmacology ; Dose-Response Relationship, Drug ; DT-diaphorase ; Fundamental and applied biological sciences. Psychology ; Genetics of eukaryotes. Biological and molecular evolution ; Medical sciences ; Metabolism ; Mice ; Micronucleus Tests ; Mutagenesis ; Mutagenicity ; Mutagenicity Tests ; Mutagens - toxicity ; NAD(P)H Dehydrogenase (Quinone) - metabolism ; NADP - chemistry ; Olea ; Oxidative Stress ; Salmonella ; Salmonella typhimurium ; Salmonella typhimurium - genetics ; Toxicity ; Toxicology</subject><ispartof>Mutation research, 2011-05, Vol.722 (1), p.39-43</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>2011 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV May 18, 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-4a46d056ceae476e2cbd17ff3dbecb5661a95107905346503754259ab31810eb3</citedby><cites>FETCH-LOGICAL-c456t-4a46d056ceae476e2cbd17ff3dbecb5661a95107905346503754259ab31810eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1383571811000623$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24241803$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21354327$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Zhaohui</creatorcontrib><creatorcontrib>Fu, Juanling</creatorcontrib><creatorcontrib>Yao, Biyun</creatorcontrib><creatorcontrib>Zhang, Xiaolin</creatorcontrib><creatorcontrib>Zhao, Peng</creatorcontrib><creatorcontrib>Zhou, Zongcan</creatorcontrib><title>In vitro genotoxicity of danthron and its potential mechanism</title><title>Mutation research</title><addtitle>Mutat Res</addtitle><description>To ascertain the in vitro genotoxicity of danthron and its potential mechanism of action, we performed an Ames test, a cytokinesis-block micronucleus assay and a comet assay in Balb/c 3T3 cells. The Ames test revealed that danthron was mutagenic only toward Salmonella typhimurium strain TA102 in the presence of an exogenous metabolic activation system (S9 mix). Danthron (25, 50 and 100μg/ml) increased the frequencies of micronuclear cells with or without S9 mix, and the comet length, tail length and Olive tail moment in comet assays without S9 mix in a dose-dependent manner. These results demonstrated the in vitro genotoxicity of danthron and that 3T3 cells are capable of activating danthron. When NADP was replaced by NAD in the S9 mix, danthron remained mutagenic toward strain TA102. The addition of dicoumarol, a DT-diaphorase inhibitor, decreased the number of danthron-induced histidine revertants by 35–39%, indicating that DT-diaphorase is involved in the metabolic activation of danthron in the presence of NADH as an electron donor. In 3T3 cells, increases in reactive oxygen species (ROS) formation and 8-hydroxydeoxyguanosine levels as well as a reduction in GSH levels were induced by danthron in a dose-dependent manner, indicating that oxidative stress may be a major contributing pathway in the genotoxicity of danthron.</description><subject>1,8-Dihydroxyanthraquinone</subject><subject>Animals</subject><subject>Anthraquinones - metabolism</subject><subject>Anthraquinones - toxicity</subject><subject>BALB 3T3 Cells</subject><subject>Bioassays</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Comet Assay</subject><subject>Cytokines</subject><subject>Danthron</subject><subject>Dicumarol - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>DT-diaphorase</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Micronucleus Tests</subject><subject>Mutagenesis</subject><subject>Mutagenicity</subject><subject>Mutagenicity Tests</subject><subject>Mutagens - toxicity</subject><subject>NAD(P)H Dehydrogenase (Quinone) - metabolism</subject><subject>NADP - chemistry</subject><subject>Olea</subject><subject>Oxidative Stress</subject><subject>Salmonella</subject><subject>Salmonella typhimurium</subject><subject>Salmonella typhimurium - genetics</subject><subject>Toxicity</subject><subject>Toxicology</subject><issn>1383-5718</issn><issn>0027-5107</issn><issn>1879-3592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U1rFTEUBuBBFFurf6EMgnQ148l3ZiEopdVCoZu6DpnMGZvLTHJNcov99025twpuukoWz3nz8TbNKYGeAJGfN_2afmEo8U9PgZAeaA8gXzXHRKuhY2Kgr-ueadYJRfRR8y7nDQAFBvptc0QJE5xRddx8uQrtvS8ptjUt1jjvfHlo49xONpS7FENrw9T6ktttLPVAb5d2RXdng8_r--bNbJeMHw7rSfPz8uL2_Ed3ffP96vzbdee4kKXjlssJhHRokSuJ1I0TUfPMphHdKKQkdhAE1ACCcSmAKcGpGOzIiCaAIztpzva52xR_7zAXs_rscFlswLjLRuvqQAzDy1JqpiQdaJUf_5ObuEuhPsNoxZgGoqAiuUcuxZwTzmab_GrTgyFgnoowG_NchHkqwgA1tYg6eHpI340rTn_Hnn--gk8HYLOzy5xscD7_c5xyooFV93XvsP7vvcdksvMYHE4-oStmiv6luzwCuEuoZA</recordid><startdate>20110518</startdate><enddate>20110518</enddate><creator>Zhang, Zhaohui</creator><creator>Fu, Juanling</creator><creator>Yao, Biyun</creator><creator>Zhang, Xiaolin</creator><creator>Zhao, Peng</creator><creator>Zhou, Zongcan</creator><general>Elsevier B.V</general><general>Elsevier</general><general>Elsevier BV</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>7ST</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope></search><sort><creationdate>20110518</creationdate><title>In vitro genotoxicity of danthron and its potential mechanism</title><author>Zhang, Zhaohui ; Fu, Juanling ; Yao, Biyun ; Zhang, Xiaolin ; Zhao, Peng ; Zhou, Zongcan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-4a46d056ceae476e2cbd17ff3dbecb5661a95107905346503754259ab31810eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>1,8-Dihydroxyanthraquinone</topic><topic>Animals</topic><topic>Anthraquinones - metabolism</topic><topic>Anthraquinones - toxicity</topic><topic>BALB 3T3 Cells</topic><topic>Bioassays</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Comet Assay</topic><topic>Cytokines</topic><topic>Danthron</topic><topic>Dicumarol - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>DT-diaphorase</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Micronucleus Tests</topic><topic>Mutagenesis</topic><topic>Mutagenicity</topic><topic>Mutagenicity Tests</topic><topic>Mutagens - toxicity</topic><topic>NAD(P)H Dehydrogenase (Quinone) - metabolism</topic><topic>NADP - chemistry</topic><topic>Olea</topic><topic>Oxidative Stress</topic><topic>Salmonella</topic><topic>Salmonella typhimurium</topic><topic>Salmonella typhimurium - genetics</topic><topic>Toxicity</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Zhaohui</creatorcontrib><creatorcontrib>Fu, Juanling</creatorcontrib><creatorcontrib>Yao, Biyun</creatorcontrib><creatorcontrib>Zhang, Xiaolin</creatorcontrib><creatorcontrib>Zhao, Peng</creatorcontrib><creatorcontrib>Zhou, Zongcan</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>Environment Abstracts</collection><collection>Nucleic Acids Abstracts</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><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Mutation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Zhaohui</au><au>Fu, Juanling</au><au>Yao, Biyun</au><au>Zhang, Xiaolin</au><au>Zhao, Peng</au><au>Zhou, Zongcan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro genotoxicity of danthron and its potential mechanism</atitle><jtitle>Mutation research</jtitle><addtitle>Mutat Res</addtitle><date>2011-05-18</date><risdate>2011</risdate><volume>722</volume><issue>1</issue><spage>39</spage><epage>43</epage><pages>39-43</pages><issn>1383-5718</issn><issn>0027-5107</issn><eissn>1879-3592</eissn><abstract>To ascertain the in vitro genotoxicity of danthron and its potential mechanism of action, we performed an Ames test, a cytokinesis-block micronucleus assay and a comet assay in Balb/c 3T3 cells. The Ames test revealed that danthron was mutagenic only toward Salmonella typhimurium strain TA102 in the presence of an exogenous metabolic activation system (S9 mix). Danthron (25, 50 and 100μg/ml) increased the frequencies of micronuclear cells with or without S9 mix, and the comet length, tail length and Olive tail moment in comet assays without S9 mix in a dose-dependent manner. These results demonstrated the in vitro genotoxicity of danthron and that 3T3 cells are capable of activating danthron. When NADP was replaced by NAD in the S9 mix, danthron remained mutagenic toward strain TA102. The addition of dicoumarol, a DT-diaphorase inhibitor, decreased the number of danthron-induced histidine revertants by 35–39%, indicating that DT-diaphorase is involved in the metabolic activation of danthron in the presence of NADH as an electron donor. In 3T3 cells, increases in reactive oxygen species (ROS) formation and 8-hydroxydeoxyguanosine levels as well as a reduction in GSH levels were induced by danthron in a dose-dependent manner, indicating that oxidative stress may be a major contributing pathway in the genotoxicity of danthron.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21354327</pmid><doi>10.1016/j.mrgentox.2011.02.006</doi><tpages>5</tpages></addata></record> |
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subjects | 1,8-Dihydroxyanthraquinone Animals Anthraquinones - metabolism Anthraquinones - toxicity BALB 3T3 Cells Bioassays Biological and medical sciences Biotransformation Comet Assay Cytokines Danthron Dicumarol - pharmacology Dose-Response Relationship, Drug DT-diaphorase Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Medical sciences Metabolism Mice Micronucleus Tests Mutagenesis Mutagenicity Mutagenicity Tests Mutagens - toxicity NAD(P)H Dehydrogenase (Quinone) - metabolism NADP - chemistry Olea Oxidative Stress Salmonella Salmonella typhimurium Salmonella typhimurium - genetics Toxicity Toxicology |
title | In vitro genotoxicity of danthron and its potential mechanism |
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