Studies on the Toxicity and Radiosensitizing Ability of Misonidazole under Conditions of Prolonged Incubation
In vitro studies with CHO cells indicate that the 2-nitroimidazole, misonidazole, is markedly more toxic under hypoxic conditions than under aerobic conditions. Also, survival curves determined using prolonged exposure to the drug under hypoxic conditions before irradiation have shown a reduction in...
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| Veröffentlicht in: | Radiat. Res.; (United States) 1978-09, Vol.75 (3), p.541-555 |
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| creator | Wong, T. W. Whitmore, G. F. Gulyas, S. |
| description | In vitro studies with CHO cells indicate that the 2-nitroimidazole, misonidazole, is markedly more toxic under hypoxic conditions than under aerobic conditions. Also, survival curves determined using prolonged exposure to the drug under hypoxic conditions before irradiation have shown a reduction in the extrapolation number (ñ) as well as the mean lethal dose (D0). Studies with radioactive misonidazole have indicated that at 37°C there is a gradual accumulation of radioactive material within hypoxic as compared to aerobic cells and that over an incubation period of 5 hr, a 2- to 3-fold increase in uptake by hypoxic cells is observed. Chromatographic analysis has shown that this increase in uptake is due to the accumulation of metabolites of misonidazole. It is suggested that both the increase in toxicity and reduction in ñ as a result of prolonged incubation with misonidazole under hypoxic conditions are related to the formation of these metabolites. |
| doi_str_mv | 10.2307/3574841 |
| format | Article |
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W. ; Whitmore, G. F. ; Gulyas, S.</creator><creatorcontrib>Wong, T. W. ; Whitmore, G. F. ; Gulyas, S. ; Ontario Cancer Inst., Toronto</creatorcontrib><description>In vitro studies with CHO cells indicate that the 2-nitroimidazole, misonidazole, is markedly more toxic under hypoxic conditions than under aerobic conditions. Also, survival curves determined using prolonged exposure to the drug under hypoxic conditions before irradiation have shown a reduction in the extrapolation number (ñ) as well as the mean lethal dose (D0). Studies with radioactive misonidazole have indicated that at 37°C there is a gradual accumulation of radioactive material within hypoxic as compared to aerobic cells and that over an incubation period of 5 hr, a 2- to 3-fold increase in uptake by hypoxic cells is observed. Chromatographic analysis has shown that this increase in uptake is due to the accumulation of metabolites of misonidazole. It is suggested that both the increase in toxicity and reduction in ñ as a result of prolonged incubation with misonidazole under hypoxic conditions are related to the formation of these metabolites.</description><identifier>ISSN: 0033-7587</identifier><identifier>EISSN: 1938-5404</identifier><identifier>DOI: 10.2307/3574841</identifier><identifier>PMID: 724984</identifier><language>eng</language><publisher>United States: Academic Press, Inc</publisher><subject>Aerobic conditions ; Anaerobic conditions ; ANIMAL CELLS ; ANIMALS ; ANOXIA ; AZOLES ; BETA DECAY RADIOISOTOPES ; BETA-MINUS DECAY RADIOISOTOPES ; CELL CULTURES ; Cell Survival - drug effects ; Cell Survival - radiation effects ; Cells, Cultured - drug effects ; CHO cells ; Chromatography ; COBALT 60 ; COBALT ISOTOPES ; Cobalt Radioisotopes ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; DRUGS ; ELECTROMAGNETIC RADIATION ; GAMMA RADIATION ; HAMSTERS ; HETEROCYCLIC COMPOUNDS ; Hypoxia ; IMIDAZOLES ; IN VITRO ; INTERMEDIATE MASS NUCLEI ; INTERNAL CONVERSION RADIOISOTOPES ; IONIZING RADIATIONS ; IRRADIATION ; ISOMERIC TRANSITION ISOTOPES ; ISOTOPES ; MAMMALS ; Mathematical extrapolation ; METABOLITES ; MINUTES LIVING RADIOISOTOPES ; Misonidazole - metabolism ; Misonidazole - pharmacology ; Misonidazole - toxicity ; Nitroimidazoles - toxicity ; NUCLEI ; ODD-ODD NUCLEI ; ORGANIC COMPOUNDS ; ORGANIC NITROGEN COMPOUNDS ; Radiation Tolerance ; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT ; RADIATIONS ; Radioactive decay ; RADIOISOTOPES ; RADIOSENSITIVITY ; RADIOSENSITIVITY EFFECTS ; RADIOSENSITIZERS ; RESPONSE MODIFYING FACTORS ; RODENTS ; Temperature ; Time Factors ; TOXICITY ; Tumors ; VERTEBRATES ; Washing ; YEARS LIVING RADIOISOTOPES 560121 -- Radiation Effects on Cells-- External Source-- (-1987)</subject><ispartof>Radiat. Res.; (United States), 1978-09, Vol.75 (3), p.541-555</ispartof><rights>Copyright 1978 Academic Press, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-49d3c409825ce40e728acaf3c316e5fe2c87343f70287619c936a908a67bdb6a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3574841$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3574841$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/724984$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/6586547$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, T. W.</creatorcontrib><creatorcontrib>Whitmore, G. F.</creatorcontrib><creatorcontrib>Gulyas, S.</creatorcontrib><creatorcontrib>Ontario Cancer Inst., Toronto</creatorcontrib><title>Studies on the Toxicity and Radiosensitizing Ability of Misonidazole under Conditions of Prolonged Incubation</title><title>Radiat. Res.; (United States)</title><addtitle>Radiat Res</addtitle><description>In vitro studies with CHO cells indicate that the 2-nitroimidazole, misonidazole, is markedly more toxic under hypoxic conditions than under aerobic conditions. Also, survival curves determined using prolonged exposure to the drug under hypoxic conditions before irradiation have shown a reduction in the extrapolation number (ñ) as well as the mean lethal dose (D0). Studies with radioactive misonidazole have indicated that at 37°C there is a gradual accumulation of radioactive material within hypoxic as compared to aerobic cells and that over an incubation period of 5 hr, a 2- to 3-fold increase in uptake by hypoxic cells is observed. Chromatographic analysis has shown that this increase in uptake is due to the accumulation of metabolites of misonidazole. It is suggested that both the increase in toxicity and reduction in ñ as a result of prolonged incubation with misonidazole under hypoxic conditions are related to the formation of these metabolites.</description><subject>Aerobic conditions</subject><subject>Anaerobic conditions</subject><subject>ANIMAL CELLS</subject><subject>ANIMALS</subject><subject>ANOXIA</subject><subject>AZOLES</subject><subject>BETA DECAY RADIOISOTOPES</subject><subject>BETA-MINUS DECAY RADIOISOTOPES</subject><subject>CELL CULTURES</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - radiation effects</subject><subject>Cells, Cultured - drug effects</subject><subject>CHO cells</subject><subject>Chromatography</subject><subject>COBALT 60</subject><subject>COBALT ISOTOPES</subject><subject>Cobalt Radioisotopes</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dose-Response Relationship, Radiation</subject><subject>DRUGS</subject><subject>ELECTROMAGNETIC RADIATION</subject><subject>GAMMA RADIATION</subject><subject>HAMSTERS</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>Hypoxia</subject><subject>IMIDAZOLES</subject><subject>IN VITRO</subject><subject>INTERMEDIATE MASS NUCLEI</subject><subject>INTERNAL CONVERSION RADIOISOTOPES</subject><subject>IONIZING RADIATIONS</subject><subject>IRRADIATION</subject><subject>ISOMERIC TRANSITION ISOTOPES</subject><subject>ISOTOPES</subject><subject>MAMMALS</subject><subject>Mathematical extrapolation</subject><subject>METABOLITES</subject><subject>MINUTES LIVING RADIOISOTOPES</subject><subject>Misonidazole - metabolism</subject><subject>Misonidazole - pharmacology</subject><subject>Misonidazole - toxicity</subject><subject>Nitroimidazoles - toxicity</subject><subject>NUCLEI</subject><subject>ODD-ODD NUCLEI</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC NITROGEN COMPOUNDS</subject><subject>Radiation Tolerance</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</subject><subject>RADIATIONS</subject><subject>Radioactive decay</subject><subject>RADIOISOTOPES</subject><subject>RADIOSENSITIVITY</subject><subject>RADIOSENSITIVITY EFFECTS</subject><subject>RADIOSENSITIZERS</subject><subject>RESPONSE MODIFYING FACTORS</subject><subject>RODENTS</subject><subject>Temperature</subject><subject>Time Factors</subject><subject>TOXICITY</subject><subject>Tumors</subject><subject>VERTEBRATES</subject><subject>Washing</subject><subject>YEARS LIVING RADIOISOTOPES 560121 -- Radiation Effects on Cells-- External Source-- (-1987)</subject><issn>0033-7587</issn><issn>1938-5404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1978</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kF1LwzAUhoP4Naf4B7wIInhVTZq0SS7H8GMwUXRelzRJt4wuGU0Kbr_elg7vvDocnoeXc14ArjF6SAlijyRjlFN8BEZYEJ5kFNFjMEKIkIRlnJ2DixDWqNtxLs7AKUup4HQENl-x1dYE6B2MKwMX_scqG3dQOg0_pbY-GBdstHvrlnBS2rqHvoJvNnhntdz72sDWadPAqXe6M70LvfDR-Nq7pdFw5lRbyh5cgpNK1sFcHeYYfD8_Laavyfz9ZTadzBNFCI4JFZooigRPM2UoMizlUsmKqO54k1UmVZwRSiqGUs5yLJQguRSIy5yVuswlGYPbIdeHaIvQPWTUSnnnjIpFnvE8o6yT7gdJNT6ExlTFtrEb2ewKjIq-0-LQaWfeDOa2LTdG_3lDiR2-G_A6RN_8m_ILt818wQ</recordid><startdate>197809</startdate><enddate>197809</enddate><creator>Wong, T. W.</creator><creator>Whitmore, G. F.</creator><creator>Gulyas, S.</creator><general>Academic Press, 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><scope>OTOTI</scope></search><sort><creationdate>197809</creationdate><title>Studies on the Toxicity and Radiosensitizing Ability of Misonidazole under Conditions of Prolonged Incubation</title><author>Wong, T. W. ; Whitmore, G. F. ; Gulyas, S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-49d3c409825ce40e728acaf3c316e5fe2c87343f70287619c936a908a67bdb6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1978</creationdate><topic>Aerobic conditions</topic><topic>Anaerobic conditions</topic><topic>ANIMAL CELLS</topic><topic>ANIMALS</topic><topic>ANOXIA</topic><topic>AZOLES</topic><topic>BETA DECAY RADIOISOTOPES</topic><topic>BETA-MINUS DECAY RADIOISOTOPES</topic><topic>CELL CULTURES</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - radiation effects</topic><topic>Cells, Cultured - drug effects</topic><topic>CHO cells</topic><topic>Chromatography</topic><topic>COBALT 60</topic><topic>COBALT ISOTOPES</topic><topic>Cobalt Radioisotopes</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dose-Response Relationship, Radiation</topic><topic>DRUGS</topic><topic>ELECTROMAGNETIC RADIATION</topic><topic>GAMMA RADIATION</topic><topic>HAMSTERS</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>Hypoxia</topic><topic>IMIDAZOLES</topic><topic>IN VITRO</topic><topic>INTERMEDIATE MASS NUCLEI</topic><topic>INTERNAL CONVERSION RADIOISOTOPES</topic><topic>IONIZING RADIATIONS</topic><topic>IRRADIATION</topic><topic>ISOMERIC TRANSITION ISOTOPES</topic><topic>ISOTOPES</topic><topic>MAMMALS</topic><topic>Mathematical extrapolation</topic><topic>METABOLITES</topic><topic>MINUTES LIVING RADIOISOTOPES</topic><topic>Misonidazole - metabolism</topic><topic>Misonidazole - pharmacology</topic><topic>Misonidazole - toxicity</topic><topic>Nitroimidazoles - toxicity</topic><topic>NUCLEI</topic><topic>ODD-ODD NUCLEI</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC NITROGEN COMPOUNDS</topic><topic>Radiation Tolerance</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</topic><topic>RADIATIONS</topic><topic>Radioactive decay</topic><topic>RADIOISOTOPES</topic><topic>RADIOSENSITIVITY</topic><topic>RADIOSENSITIVITY EFFECTS</topic><topic>RADIOSENSITIZERS</topic><topic>RESPONSE MODIFYING FACTORS</topic><topic>RODENTS</topic><topic>Temperature</topic><topic>Time Factors</topic><topic>TOXICITY</topic><topic>Tumors</topic><topic>VERTEBRATES</topic><topic>Washing</topic><topic>YEARS LIVING RADIOISOTOPES 560121 -- Radiation Effects on Cells-- External Source-- (-1987)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, T. W.</creatorcontrib><creatorcontrib>Whitmore, G. F.</creatorcontrib><creatorcontrib>Gulyas, S.</creatorcontrib><creatorcontrib>Ontario Cancer Inst., Toronto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>Radiat. Res.; (United States)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, T. W.</au><au>Whitmore, G. F.</au><au>Gulyas, S.</au><aucorp>Ontario Cancer Inst., Toronto</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Studies on the Toxicity and Radiosensitizing Ability of Misonidazole under Conditions of Prolonged Incubation</atitle><jtitle>Radiat. Res.; (United States)</jtitle><addtitle>Radiat Res</addtitle><date>1978-09</date><risdate>1978</risdate><volume>75</volume><issue>3</issue><spage>541</spage><epage>555</epage><pages>541-555</pages><issn>0033-7587</issn><eissn>1938-5404</eissn><abstract>In vitro studies with CHO cells indicate that the 2-nitroimidazole, misonidazole, is markedly more toxic under hypoxic conditions than under aerobic conditions. Also, survival curves determined using prolonged exposure to the drug under hypoxic conditions before irradiation have shown a reduction in the extrapolation number (ñ) as well as the mean lethal dose (D0). Studies with radioactive misonidazole have indicated that at 37°C there is a gradual accumulation of radioactive material within hypoxic as compared to aerobic cells and that over an incubation period of 5 hr, a 2- to 3-fold increase in uptake by hypoxic cells is observed. Chromatographic analysis has shown that this increase in uptake is due to the accumulation of metabolites of misonidazole. It is suggested that both the increase in toxicity and reduction in ñ as a result of prolonged incubation with misonidazole under hypoxic conditions are related to the formation of these metabolites.</abstract><cop>United States</cop><pub>Academic Press, Inc</pub><pmid>724984</pmid><doi>10.2307/3574841</doi><tpages>15</tpages></addata></record> |
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| ispartof | Radiat. Res.; (United States), 1978-09, Vol.75 (3), p.541-555 |
| issn | 0033-7587 1938-5404 |
| language | eng |
| recordid | cdi_crossref_primary_10_2307_3574841 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing |
| subjects | Aerobic conditions Anaerobic conditions ANIMAL CELLS ANIMALS ANOXIA AZOLES BETA DECAY RADIOISOTOPES BETA-MINUS DECAY RADIOISOTOPES CELL CULTURES Cell Survival - drug effects Cell Survival - radiation effects Cells, Cultured - drug effects CHO cells Chromatography COBALT 60 COBALT ISOTOPES Cobalt Radioisotopes Dose-Response Relationship, Drug Dose-Response Relationship, Radiation DRUGS ELECTROMAGNETIC RADIATION GAMMA RADIATION HAMSTERS HETEROCYCLIC COMPOUNDS Hypoxia IMIDAZOLES IN VITRO INTERMEDIATE MASS NUCLEI INTERNAL CONVERSION RADIOISOTOPES IONIZING RADIATIONS IRRADIATION ISOMERIC TRANSITION ISOTOPES ISOTOPES MAMMALS Mathematical extrapolation METABOLITES MINUTES LIVING RADIOISOTOPES Misonidazole - metabolism Misonidazole - pharmacology Misonidazole - toxicity Nitroimidazoles - toxicity NUCLEI ODD-ODD NUCLEI ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS Radiation Tolerance RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT RADIATIONS Radioactive decay RADIOISOTOPES RADIOSENSITIVITY RADIOSENSITIVITY EFFECTS RADIOSENSITIZERS RESPONSE MODIFYING FACTORS RODENTS Temperature Time Factors TOXICITY Tumors VERTEBRATES Washing YEARS LIVING RADIOISOTOPES 560121 -- Radiation Effects on Cells-- External Source-- (-1987) |
| title | Studies on the Toxicity and Radiosensitizing Ability of Misonidazole under Conditions of Prolonged Incubation |
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