Comparison of binding of [3H]misonidazole and [14C]misonidazole in multicell spheroids
Uptake of [2-ring-14C]misonidazole and [3H]misonidazole with tritium in the side chain has been compared in 1-mm EMT-6/UW spheroids using liquid scintillation counting and autoradiography. The uptake of both labeled sensitizers as a function of incubation time was virtually identical. Uptake by the...
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| Veröffentlicht in: | Radiat. Res.; (United States) 1985-03, Vol.101 (3), p.473-479 |
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| creator | Rasey, J S Grunbaum, Z Krohn, K Nelson, N Chin, L |
| description | Uptake of [2-ring-14C]misonidazole and [3H]misonidazole with tritium in the side chain has been compared in 1-mm EMT-6/UW spheroids using liquid scintillation counting and autoradiography. The uptake of both labeled sensitizers as a function of incubation time was virtually identical. Uptake by the spheroids exceeded levels in the medium by 11/2 to 2 hr and was well modeled as a first-order binding process, with rate constants of 0.00324 hr-1 for 3H and 0.00388 hr-1 for 14C. The similar uptake of the two versions of this sensitizer labeled in different positions suggests that the metabolic actions which allow the drug to bind in hypoxic cells do not principally involve metabolites which separate the number 2 carbon of the imidazole ring from the side chain. The pattern of silver grains in autoradiographs was similar for both labeled sensitizers, with most labeled drug bound in an intermediate zone of cells between the necrotic center and the actively proliferating rim of the spheroids. The superior resolution possible with the tritiated compound showed that both nucleus and cytoplasm in viable looking cells were labeled while pycnotic cells were not labeled. |
| doi_str_mv | 10.2307/3576506 |
| format | Article |
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The uptake of both labeled sensitizers as a function of incubation time was virtually identical. Uptake by the spheroids exceeded levels in the medium by 11/2 to 2 hr and was well modeled as a first-order binding process, with rate constants of 0.00324 hr-1 for 3H and 0.00388 hr-1 for 14C. The similar uptake of the two versions of this sensitizer labeled in different positions suggests that the metabolic actions which allow the drug to bind in hypoxic cells do not principally involve metabolites which separate the number 2 carbon of the imidazole ring from the side chain. The pattern of silver grains in autoradiographs was similar for both labeled sensitizers, with most labeled drug bound in an intermediate zone of cells between the necrotic center and the actively proliferating rim of the spheroids. The superior resolution possible with the tritiated compound showed that both nucleus and cytoplasm in viable looking cells were labeled while pycnotic cells were not labeled.</description><identifier>ISSN: 0033-7587</identifier><identifier>DOI: 10.2307/3576506</identifier><identifier>PMID: 3983363</identifier><language>eng</language><publisher>United States</publisher><subject>550601 - Medicine- Unsealed Radionuclides in Diagnostics ; ANIMAL CELLS ; Animals ; ANOXIA ; ANTINEOPLASTIC DRUGS ; AUTORADIOGRAPHY ; AZOLES ; CARBON 14 COMPOUNDS ; Carbon Radioisotopes ; CONNECTIVE TISSUE CELLS ; COUNTING TECHNIQUES ; DRUGS ; FIBROBLASTS ; HETEROCYCLIC COMPOUNDS ; IMIDAZOLES ; In Vitro Techniques ; LABELLED COMPOUNDS ; MISONIDAZOLE ; Misonidazole - metabolism ; Models, Biological ; Neoplasms, Experimental - metabolism ; Nitroimidazoles - metabolism ; ORGANIC COMPOUNDS ; ORGANIC NITROGEN COMPOUNDS ; Oxygen - physiology ; RADIATION DOSE DISTRIBUTIONS ; Radiation-Sensitizing Agents - metabolism ; RADIOLOGY AND NUCLEAR MEDICINE ; RADIOSENSITIZERS ; SCINTILLATION COUNTING ; SOMATIC CELLS ; Space life sciences ; SPATIAL DOSE DISTRIBUTIONS ; SPHEROIDS ; Tritium ; TRITIUM COMPOUNDS ; UPTAKE</subject><ispartof>Radiat. 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Res.; (United States)</title><addtitle>Radiat Res</addtitle><description>Uptake of [2-ring-14C]misonidazole and [3H]misonidazole with tritium in the side chain has been compared in 1-mm EMT-6/UW spheroids using liquid scintillation counting and autoradiography. The uptake of both labeled sensitizers as a function of incubation time was virtually identical. Uptake by the spheroids exceeded levels in the medium by 11/2 to 2 hr and was well modeled as a first-order binding process, with rate constants of 0.00324 hr-1 for 3H and 0.00388 hr-1 for 14C. The similar uptake of the two versions of this sensitizer labeled in different positions suggests that the metabolic actions which allow the drug to bind in hypoxic cells do not principally involve metabolites which separate the number 2 carbon of the imidazole ring from the side chain. The pattern of silver grains in autoradiographs was similar for both labeled sensitizers, with most labeled drug bound in an intermediate zone of cells between the necrotic center and the actively proliferating rim of the spheroids. The superior resolution possible with the tritiated compound showed that both nucleus and cytoplasm in viable looking cells were labeled while pycnotic cells were not labeled.</description><subject>550601 - Medicine- Unsealed Radionuclides in Diagnostics</subject><subject>ANIMAL CELLS</subject><subject>Animals</subject><subject>ANOXIA</subject><subject>ANTINEOPLASTIC DRUGS</subject><subject>AUTORADIOGRAPHY</subject><subject>AZOLES</subject><subject>CARBON 14 COMPOUNDS</subject><subject>Carbon Radioisotopes</subject><subject>CONNECTIVE TISSUE CELLS</subject><subject>COUNTING TECHNIQUES</subject><subject>DRUGS</subject><subject>FIBROBLASTS</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>IMIDAZOLES</subject><subject>In Vitro Techniques</subject><subject>LABELLED COMPOUNDS</subject><subject>MISONIDAZOLE</subject><subject>Misonidazole - metabolism</subject><subject>Models, Biological</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Nitroimidazoles - metabolism</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC NITROGEN COMPOUNDS</subject><subject>Oxygen - physiology</subject><subject>RADIATION DOSE DISTRIBUTIONS</subject><subject>Radiation-Sensitizing Agents - metabolism</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>RADIOSENSITIZERS</subject><subject>SCINTILLATION COUNTING</subject><subject>SOMATIC CELLS</subject><subject>Space life sciences</subject><subject>SPATIAL DOSE DISTRIBUTIONS</subject><subject>SPHEROIDS</subject><subject>Tritium</subject><subject>TRITIUM COMPOUNDS</subject><subject>UPTAKE</subject><issn>0033-7587</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE9LxDAQxXNQVl3FTyAUD3qqJpvmT49S1BUWvKiXRUKaTN1Im9SmPeint2WL4GlmHr95zDyEzgm-WVEsbikTnGF-gI4xpjQVTIojdBLjJx5nwvMFWtBcUsrpMXorQtPqzsXgk1AlpfPW-Y-p3dL1ezPpzuqfUEOivU22JCv-q84nzVD3zkBdJ7HdQRecjafosNJ1hLO5LtHrw_1LsU43z49Pxd0mNRTTPrVZbpgG0JUBDiUmDCAjXFZCciGIsdpysLrkuaWs4oyXNiuxkVTycackdIku974h9k5F43owOxO8B9MrJlcyy8QIXe2htgtfA8RejR9M92oPYYhKcMywIPkIXu9B04UYO6hU27lGd9-KYDVFq-ZoR_JithzKBuwfN-dKfwG15nYG</recordid><startdate>198503</startdate><enddate>198503</enddate><creator>Rasey, J S</creator><creator>Grunbaum, Z</creator><creator>Krohn, K</creator><creator>Nelson, N</creator><creator>Chin, L</creator><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>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>198503</creationdate><title>Comparison of binding of [3H]misonidazole and [14C]misonidazole in multicell spheroids</title><author>Rasey, J S ; Grunbaum, Z ; Krohn, K ; Nelson, N ; Chin, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c303t-d49c5aeeafce6eb015ee4168f786771cdad6edab69d35f656bd4b0c8386eafb13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>550601 - Medicine- Unsealed Radionuclides in Diagnostics</topic><topic>ANIMAL CELLS</topic><topic>Animals</topic><topic>ANOXIA</topic><topic>ANTINEOPLASTIC DRUGS</topic><topic>AUTORADIOGRAPHY</topic><topic>AZOLES</topic><topic>CARBON 14 COMPOUNDS</topic><topic>Carbon Radioisotopes</topic><topic>CONNECTIVE TISSUE CELLS</topic><topic>COUNTING TECHNIQUES</topic><topic>DRUGS</topic><topic>FIBROBLASTS</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>IMIDAZOLES</topic><topic>In Vitro Techniques</topic><topic>LABELLED COMPOUNDS</topic><topic>MISONIDAZOLE</topic><topic>Misonidazole - metabolism</topic><topic>Models, Biological</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Nitroimidazoles - metabolism</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC NITROGEN COMPOUNDS</topic><topic>Oxygen - physiology</topic><topic>RADIATION DOSE DISTRIBUTIONS</topic><topic>Radiation-Sensitizing Agents - metabolism</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>RADIOSENSITIZERS</topic><topic>SCINTILLATION COUNTING</topic><topic>SOMATIC CELLS</topic><topic>Space life sciences</topic><topic>SPATIAL DOSE DISTRIBUTIONS</topic><topic>SPHEROIDS</topic><topic>Tritium</topic><topic>TRITIUM COMPOUNDS</topic><topic>UPTAKE</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rasey, J S</creatorcontrib><creatorcontrib>Grunbaum, Z</creatorcontrib><creatorcontrib>Krohn, K</creatorcontrib><creatorcontrib>Nelson, N</creatorcontrib><creatorcontrib>Chin, L</creatorcontrib><creatorcontrib>Univ. of Washington, Seattle</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Radiat. Res.; (United States)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rasey, J S</au><au>Grunbaum, Z</au><au>Krohn, K</au><au>Nelson, N</au><au>Chin, L</au><aucorp>Univ. of Washington, Seattle</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of binding of [3H]misonidazole and [14C]misonidazole in multicell spheroids</atitle><jtitle>Radiat. Res.; (United States)</jtitle><addtitle>Radiat Res</addtitle><date>1985-03</date><risdate>1985</risdate><volume>101</volume><issue>3</issue><spage>473</spage><epage>479</epage><pages>473-479</pages><issn>0033-7587</issn><abstract>Uptake of [2-ring-14C]misonidazole and [3H]misonidazole with tritium in the side chain has been compared in 1-mm EMT-6/UW spheroids using liquid scintillation counting and autoradiography. The uptake of both labeled sensitizers as a function of incubation time was virtually identical. Uptake by the spheroids exceeded levels in the medium by 11/2 to 2 hr and was well modeled as a first-order binding process, with rate constants of 0.00324 hr-1 for 3H and 0.00388 hr-1 for 14C. The similar uptake of the two versions of this sensitizer labeled in different positions suggests that the metabolic actions which allow the drug to bind in hypoxic cells do not principally involve metabolites which separate the number 2 carbon of the imidazole ring from the side chain. The pattern of silver grains in autoradiographs was similar for both labeled sensitizers, with most labeled drug bound in an intermediate zone of cells between the necrotic center and the actively proliferating rim of the spheroids. The superior resolution possible with the tritiated compound showed that both nucleus and cytoplasm in viable looking cells were labeled while pycnotic cells were not labeled.</abstract><cop>United States</cop><pmid>3983363</pmid><doi>10.2307/3576506</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Jstor Complete Legacy |
| subjects | 550601 - Medicine- Unsealed Radionuclides in Diagnostics ANIMAL CELLS Animals ANOXIA ANTINEOPLASTIC DRUGS AUTORADIOGRAPHY AZOLES CARBON 14 COMPOUNDS Carbon Radioisotopes CONNECTIVE TISSUE CELLS COUNTING TECHNIQUES DRUGS FIBROBLASTS HETEROCYCLIC COMPOUNDS IMIDAZOLES In Vitro Techniques LABELLED COMPOUNDS MISONIDAZOLE Misonidazole - metabolism Models, Biological Neoplasms, Experimental - metabolism Nitroimidazoles - metabolism ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS Oxygen - physiology RADIATION DOSE DISTRIBUTIONS Radiation-Sensitizing Agents - metabolism RADIOLOGY AND NUCLEAR MEDICINE RADIOSENSITIZERS SCINTILLATION COUNTING SOMATIC CELLS Space life sciences SPATIAL DOSE DISTRIBUTIONS SPHEROIDS Tritium TRITIUM COMPOUNDS UPTAKE |
| title | Comparison of binding of [3H]misonidazole and [14C]misonidazole in multicell spheroids |
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