Cytotoxicity of an 125I-Labelled DNA Ligand
The subcellular distribution and cytotoxicity of a DNA-binding ligand [125I]-Hoechst 33258 following incubation of K562 cells with the drug was investigated. The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125I-decay induced cell death was also studied. Three diffe...
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| Veröffentlicht in: | Acta oncologica 2000, Vol.39 (6), p.681-685 |
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| container_title | Acta oncologica |
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| creator | KARAGIANNIS, Tom C LOBACHEVSKY, Pavel N MARTIN, Roger F |
| description | The subcellular distribution and cytotoxicity of a DNA-binding ligand [125I]-Hoechst 33258 following incubation of K562 cells with the drug was investigated. The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125I-decay induced cell death was also studied. Three different concentrations and specific activities of the drug were used to provide different ligand : DNA binding ratios. The results demonstrated a trend toward improved delivery of the ligand to the nucleus and to chromatin at higher ligand concentrations, with concomitant increased sensitivity to 125I-decay induced cytotoxicity and decreased protection by dimethyl sulphoxide. This correlation of radiobiological parameters with subcellular drug distribution is consistent with the classical dogma that attributes cytotoxicity to DNA double-stranded breakage in the vicinity of the site of decay, where the high LET nature of the damage confers minimal sensitivity to radical scavenging. |
| doi_str_mv | 10.1080/028418600750063721 |
| format | Article |
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The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125I-decay induced cell death was also studied. Three different concentrations and specific activities of the drug were used to provide different ligand : DNA binding ratios. The results demonstrated a trend toward improved delivery of the ligand to the nucleus and to chromatin at higher ligand concentrations, with concomitant increased sensitivity to 125I-decay induced cytotoxicity and decreased protection by dimethyl sulphoxide. This correlation of radiobiological parameters with subcellular drug distribution is consistent with the classical dogma that attributes cytotoxicity to DNA double-stranded breakage in the vicinity of the site of decay, where the high LET nature of the damage confers minimal sensitivity to radical scavenging.</description><identifier>ISSN: 0284-186X</identifier><identifier>EISSN: 1651-226X</identifier><identifier>DOI: 10.1080/028418600750063721</identifier><identifier>PMID: 11130004</identifier><identifier>CODEN: ACTOEL</identifier><language>eng</language><publisher>Basingstoke: Informa UK Ltd</publisher><subject>Apoptosis ; Binding Sites ; Biological and medical sciences ; Bisbenzimidazole - toxicity ; DNA Damage - genetics ; DNA, Neoplasm - drug effects ; DNA, Neoplasm - genetics ; Fluorescent Dyes - toxicity ; Humans ; Iodine Radioisotopes - toxicity ; K562 Cells - drug effects ; Ligands ; Medical sciences ; Radiopharmaceuticals - toxicity ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Technology. Biomaterials. Equipments. Material. 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The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125I-decay induced cell death was also studied. Three different concentrations and specific activities of the drug were used to provide different ligand : DNA binding ratios. The results demonstrated a trend toward improved delivery of the ligand to the nucleus and to chromatin at higher ligand concentrations, with concomitant increased sensitivity to 125I-decay induced cytotoxicity and decreased protection by dimethyl sulphoxide. This correlation of radiobiological parameters with subcellular drug distribution is consistent with the classical dogma that attributes cytotoxicity to DNA double-stranded breakage in the vicinity of the site of decay, where the high LET nature of the damage confers minimal sensitivity to radical scavenging.</description><subject>Apoptosis</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Bisbenzimidazole - toxicity</subject><subject>DNA Damage - genetics</subject><subject>DNA, Neoplasm - drug effects</subject><subject>DNA, Neoplasm - genetics</subject><subject>Fluorescent Dyes - toxicity</subject><subject>Humans</subject><subject>Iodine Radioisotopes - toxicity</subject><subject>K562 Cells - drug effects</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Radiopharmaceuticals - toxicity</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>Technology. Biomaterials. Equipments. Material. 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Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</topic><topic>Technology. Biomaterials. Equipments. Material. Instrumentation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KARAGIANNIS, Tom C</creatorcontrib><creatorcontrib>LOBACHEVSKY, Pavel N</creatorcontrib><creatorcontrib>MARTIN, Roger F</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Acta oncologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KARAGIANNIS, Tom C</au><au>LOBACHEVSKY, Pavel N</au><au>MARTIN, Roger F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity of an 125I-Labelled DNA Ligand</atitle><jtitle>Acta oncologica</jtitle><addtitle>Acta Oncol</addtitle><date>2000</date><risdate>2000</risdate><volume>39</volume><issue>6</issue><spage>681</spage><epage>685</epage><pages>681-685</pages><issn>0284-186X</issn><eissn>1651-226X</eissn><coden>ACTOEL</coden><abstract>The subcellular distribution and cytotoxicity of a DNA-binding ligand [125I]-Hoechst 33258 following incubation of K562 cells with the drug was investigated. The ability of a radical scavenger, dimethyl sulphoxide, to protect cells from the 125I-decay induced cell death was also studied. Three different concentrations and specific activities of the drug were used to provide different ligand : DNA binding ratios. The results demonstrated a trend toward improved delivery of the ligand to the nucleus and to chromatin at higher ligand concentrations, with concomitant increased sensitivity to 125I-decay induced cytotoxicity and decreased protection by dimethyl sulphoxide. This correlation of radiobiological parameters with subcellular drug distribution is consistent with the classical dogma that attributes cytotoxicity to DNA double-stranded breakage in the vicinity of the site of decay, where the high LET nature of the damage confers minimal sensitivity to radical scavenging.</abstract><cop>Basingstoke</cop><pub>Informa UK Ltd</pub><pmid>11130004</pmid><doi>10.1080/028418600750063721</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0284-186X |
| ispartof | Acta oncologica, 2000, Vol.39 (6), p.681-685 |
| issn | 0284-186X 1651-226X |
| language | eng |
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| source | MEDLINE; Taylor & Francis Journals Complete; EZB Electronic Journals Library |
| subjects | Apoptosis Binding Sites Biological and medical sciences Bisbenzimidazole - toxicity DNA Damage - genetics DNA, Neoplasm - drug effects DNA, Neoplasm - genetics Fluorescent Dyes - toxicity Humans Iodine Radioisotopes - toxicity K562 Cells - drug effects Ligands Medical sciences Radiopharmaceuticals - toxicity Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Technology. Biomaterials. Equipments. Material. Instrumentation |
| title | Cytotoxicity of an 125I-Labelled DNA Ligand |
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