Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster
► All NRTI combinations increased the frequencies of induction of mutant spots. ► Mitotic recombination was the major event induced by AZT+ddI and AZT+3TC. ► AZT+d4T showed a large discrepancy between recombination and mutation percentages. ► 3TC and d4T produced antagonism effects in combination wi...
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| Veröffentlicht in: | Food and chemical toxicology 2013-03, Vol.53, p.299-309 |
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| creator | Guimarães, N.N. Silva, C.J. de Andrade, H.H.R. Dihl, R.R. Lehmann, M. Cunha, K.S. |
| description | ► All NRTI combinations increased the frequencies of induction of mutant spots. ► Mitotic recombination was the major event induced by AZT+ddI and AZT+3TC. ► AZT+d4T showed a large discrepancy between recombination and mutation percentages. ► 3TC and d4T produced antagonism effects in combination with AZT. ► ddI showed synergistic effects in combination with AZT.
Nucleoside reverse-transcriptase inhibitor (NRTI) drugs are a major component of highly-active antiretroviral therapy (HAART). NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count, thereby showing clear clinical benefits. Therefore, the secondary effects caused by the combination of two NRTIs, mainly those related to amplification of genotoxic effects, due to increased risk of DNA damage caused by these drugs, should be carefully examined. We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT+ddI, AZT+3TC and AZT+d4T. Our results showed that all combinations increased the frequencies of induction of mutant spots. The combinations AZT+ddI and AZT+3TC were shown to induce recombination rates ranging from 86.38% to 98.36% while AZT+d4T showed a large discrepancy between recombination and mutation percentages. The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT. |
| doi_str_mv | 10.1016/j.fct.2012.12.005 |
| format | Article |
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Nucleoside reverse-transcriptase inhibitor (NRTI) drugs are a major component of highly-active antiretroviral therapy (HAART). NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count, thereby showing clear clinical benefits. Therefore, the secondary effects caused by the combination of two NRTIs, mainly those related to amplification of genotoxic effects, due to increased risk of DNA damage caused by these drugs, should be carefully examined. We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT+ddI, AZT+3TC and AZT+d4T. Our results showed that all combinations increased the frequencies of induction of mutant spots. The combinations AZT+ddI and AZT+3TC were shown to induce recombination rates ranging from 86.38% to 98.36% while AZT+d4T showed a large discrepancy between recombination and mutation percentages. The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2012.12.005</identifier><identifier>PMID: 23261680</identifier><identifier>CODEN: FCTOD7</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>3TC ; Animals ; Anti-HIV Agents - adverse effects ; antiretroviral agents ; Antiviral Agents - adverse effects ; AZT ; Biological and medical sciences ; CD4 Lymphocyte Count ; d4T ; ddI ; Didanosine - adverse effects ; DNA damage ; DNA Damage - drug effects ; Dose-Response Relationship, Drug ; Drosophila melanogaster ; Drosophila melanogaster - drug effects ; Drosophila melanogaster - metabolism ; Drug Combinations ; drugs ; Female ; genotoxicity ; Lamivudine - adverse effects ; Male ; Medical sciences ; Mitosis ; mutants ; Mutation ; NRTI ; nucleosides ; Recombinant Proteins ; risk ; SMART ; somatic cells ; synergism ; therapeutics ; Toxicology ; viremia ; Wings, Animal - drug effects ; Zidovudine - adverse effects</subject><ispartof>Food and chemical toxicology, 2013-03, Vol.53, p.299-309</ispartof><rights>2012 Elsevier Ltd</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-5a04db970d642234576c5f7b4f498293d0244779d14d746f77eb2fa6295c762f3</citedby><cites>FETCH-LOGICAL-c483t-5a04db970d642234576c5f7b4f498293d0244779d14d746f77eb2fa6295c762f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0278691512008678$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27058864$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23261680$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guimarães, N.N.</creatorcontrib><creatorcontrib>Silva, C.J.</creatorcontrib><creatorcontrib>de Andrade, H.H.R.</creatorcontrib><creatorcontrib>Dihl, R.R.</creatorcontrib><creatorcontrib>Lehmann, M.</creatorcontrib><creatorcontrib>Cunha, K.S.</creatorcontrib><title>Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>► All NRTI combinations increased the frequencies of induction of mutant spots. ► Mitotic recombination was the major event induced by AZT+ddI and AZT+3TC. ► AZT+d4T showed a large discrepancy between recombination and mutation percentages. ► 3TC and d4T produced antagonism effects in combination with AZT. ► ddI showed synergistic effects in combination with AZT.
Nucleoside reverse-transcriptase inhibitor (NRTI) drugs are a major component of highly-active antiretroviral therapy (HAART). NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count, thereby showing clear clinical benefits. Therefore, the secondary effects caused by the combination of two NRTIs, mainly those related to amplification of genotoxic effects, due to increased risk of DNA damage caused by these drugs, should be carefully examined. We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT+ddI, AZT+3TC and AZT+d4T. Our results showed that all combinations increased the frequencies of induction of mutant spots. The combinations AZT+ddI and AZT+3TC were shown to induce recombination rates ranging from 86.38% to 98.36% while AZT+d4T showed a large discrepancy between recombination and mutation percentages. The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT.</description><subject>3TC</subject><subject>Animals</subject><subject>Anti-HIV Agents - adverse effects</subject><subject>antiretroviral agents</subject><subject>Antiviral Agents - adverse effects</subject><subject>AZT</subject><subject>Biological and medical sciences</subject><subject>CD4 Lymphocyte Count</subject><subject>d4T</subject><subject>ddI</subject><subject>Didanosine - adverse effects</subject><subject>DNA damage</subject><subject>DNA Damage - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drosophila melanogaster</subject><subject>Drosophila melanogaster - drug effects</subject><subject>Drosophila melanogaster - metabolism</subject><subject>Drug Combinations</subject><subject>drugs</subject><subject>Female</subject><subject>genotoxicity</subject><subject>Lamivudine - adverse effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mitosis</subject><subject>mutants</subject><subject>Mutation</subject><subject>NRTI</subject><subject>nucleosides</subject><subject>Recombinant Proteins</subject><subject>risk</subject><subject>SMART</subject><subject>somatic cells</subject><subject>synergism</subject><subject>therapeutics</subject><subject>Toxicology</subject><subject>viremia</subject><subject>Wings, Animal - drug effects</subject><subject>Zidovudine - adverse effects</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9rFDEYh0NR7Lb6AXrRuRR6mTXJ5M8MnspqW6HgQXsO72SSNctMsibZpfvtzbhbvQkvBMLz_vLjCUJXBC8JJuLjZml1XlJM6LIMxvwMLUgrm1o0nLxCC0xlW4uO8HN0kdIGYyyJFG_QOW2oIKLFC5RWYdpChOz2pgIP4yG5VAVbrY032ekqh2enXT7Md-CziybHsHcRxkqHqXe-rAafKuerFCaYV7QZxz8Zn2NIYfvTjVBNZgQf1pCyiW_RawtjMu9O5yV6uvvyY_VQP367_7q6faw1a5tcc8Bs6DuJB8EobRiXQnMre2ZZ19KuGTBlTMpuIGyQTFgpTU8tCNpxLQW1zSW6OeZuY_i1MymryaW5HHgTdkkRIUXDZj8FJUdUl8opGqu20U0QD4pgNbtWG1Vcq9m1KlNcl533p_hdP5nh78aL3AJcnwBIGkYbwWuX_nES87YVrHAfjpyFoGAdC_P0vbzEMSaScjEnfToSpujaOxNV0s54bYbyH6XWENx_iv4GXHWmiA</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Guimarães, N.N.</creator><creator>Silva, C.J.</creator><creator>de Andrade, H.H.R.</creator><creator>Dihl, R.R.</creator><creator>Lehmann, M.</creator><creator>Cunha, K.S.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>7SS</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20130301</creationdate><title>Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster</title><author>Guimarães, N.N. ; Silva, C.J. ; de Andrade, H.H.R. ; Dihl, R.R. ; Lehmann, M. ; Cunha, K.S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-5a04db970d642234576c5f7b4f498293d0244779d14d746f77eb2fa6295c762f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3TC</topic><topic>Animals</topic><topic>Anti-HIV Agents - adverse effects</topic><topic>antiretroviral agents</topic><topic>Antiviral Agents - adverse effects</topic><topic>AZT</topic><topic>Biological and medical sciences</topic><topic>CD4 Lymphocyte Count</topic><topic>d4T</topic><topic>ddI</topic><topic>Didanosine - adverse effects</topic><topic>DNA damage</topic><topic>DNA Damage - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drosophila melanogaster</topic><topic>Drosophila melanogaster - drug effects</topic><topic>Drosophila melanogaster - metabolism</topic><topic>Drug Combinations</topic><topic>drugs</topic><topic>Female</topic><topic>genotoxicity</topic><topic>Lamivudine - adverse effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mitosis</topic><topic>mutants</topic><topic>Mutation</topic><topic>NRTI</topic><topic>nucleosides</topic><topic>Recombinant Proteins</topic><topic>risk</topic><topic>SMART</topic><topic>somatic cells</topic><topic>synergism</topic><topic>therapeutics</topic><topic>Toxicology</topic><topic>viremia</topic><topic>Wings, Animal - drug effects</topic><topic>Zidovudine - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guimarães, N.N.</creatorcontrib><creatorcontrib>Silva, C.J.</creatorcontrib><creatorcontrib>de Andrade, H.H.R.</creatorcontrib><creatorcontrib>Dihl, R.R.</creatorcontrib><creatorcontrib>Lehmann, M.</creatorcontrib><creatorcontrib>Cunha, K.S.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</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>Entomology Abstracts (Full archive)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS 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>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guimarães, N.N.</au><au>Silva, C.J.</au><au>de Andrade, H.H.R.</au><au>Dihl, R.R.</au><au>Lehmann, M.</au><au>Cunha, K.S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>53</volume><spage>299</spage><epage>309</epage><pages>299-309</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><coden>FCTOD7</coden><abstract>► All NRTI combinations increased the frequencies of induction of mutant spots. ► Mitotic recombination was the major event induced by AZT+ddI and AZT+3TC. ► AZT+d4T showed a large discrepancy between recombination and mutation percentages. ► 3TC and d4T produced antagonism effects in combination with AZT. ► ddI showed synergistic effects in combination with AZT.
Nucleoside reverse-transcriptase inhibitor (NRTI) drugs are a major component of highly-active antiretroviral therapy (HAART). NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count, thereby showing clear clinical benefits. Therefore, the secondary effects caused by the combination of two NRTIs, mainly those related to amplification of genotoxic effects, due to increased risk of DNA damage caused by these drugs, should be carefully examined. We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT+ddI, AZT+3TC and AZT+d4T. Our results showed that all combinations increased the frequencies of induction of mutant spots. The combinations AZT+ddI and AZT+3TC were shown to induce recombination rates ranging from 86.38% to 98.36% while AZT+d4T showed a large discrepancy between recombination and mutation percentages. The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>23261680</pmid><doi>10.1016/j.fct.2012.12.005</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3TC Animals Anti-HIV Agents - adverse effects antiretroviral agents Antiviral Agents - adverse effects AZT Biological and medical sciences CD4 Lymphocyte Count d4T ddI Didanosine - adverse effects DNA damage DNA Damage - drug effects Dose-Response Relationship, Drug Drosophila melanogaster Drosophila melanogaster - drug effects Drosophila melanogaster - metabolism Drug Combinations drugs Female genotoxicity Lamivudine - adverse effects Male Medical sciences Mitosis mutants Mutation NRTI nucleosides Recombinant Proteins risk SMART somatic cells synergism therapeutics Toxicology viremia Wings, Animal - drug effects Zidovudine - adverse effects |
| title | Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster |
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