Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine
Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incuba...
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| Veröffentlicht in: | European journal of nuclear medicine and molecular imaging 2006-05, Vol.33 (5), p.613-620 |
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| container_title | European journal of nuclear medicine and molecular imaging |
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| creator | Perillo-Adamer, Florence Delaloye, Angelika Bischof Genton, Céline S Schaffland, Andreas O Dupertuis, Yves M Buchegger, Franz |
| description | Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations.
Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment.
The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline.
FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles. |
| doi_str_mv | 10.1007/s00259-005-0009-y |
| format | Article |
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Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment.
The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline.
FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-005-0009-y</identifier><identifier>PMID: 16450135</identifier><language>eng</language><publisher>Germany: Springer Nature B.V</publisher><subject>Cell Cycle - drug effects ; Cell Cycle - radiation effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Floxuridine - administration & dosage ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Humans ; Idoxuridine - pharmacokinetics ; Iodine Radioisotopes - pharmacokinetics ; Metabolic Clearance Rate - drug effects ; Radiopharmaceuticals - pharmacokinetics</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2006-05, Vol.33 (5), p.613-620</ispartof><rights>Springer-Verlag 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c214y-46406a57dace773708c04db23ca74f311ded0a1064e8a8d30911c6e793fe7b53</citedby><cites>FETCH-LOGICAL-c214y-46406a57dace773708c04db23ca74f311ded0a1064e8a8d30911c6e793fe7b53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16450135$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perillo-Adamer, Florence</creatorcontrib><creatorcontrib>Delaloye, Angelika Bischof</creatorcontrib><creatorcontrib>Genton, Céline S</creatorcontrib><creatorcontrib>Schaffland, Andreas O</creatorcontrib><creatorcontrib>Dupertuis, Yves M</creatorcontrib><creatorcontrib>Buchegger, Franz</creatorcontrib><title>Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations.
Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment.
The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline.
FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles.</description><subject>Cell Cycle - drug effects</subject><subject>Cell Cycle - radiation effects</subject><subject>Cell Line, Tumor</subject><subject>Dose-Response Relationship, Drug</subject><subject>Floxuridine - administration & dosage</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - pathology</subject><subject>Humans</subject><subject>Idoxuridine - pharmacokinetics</subject><subject>Iodine Radioisotopes - pharmacokinetics</subject><subject>Metabolic Clearance Rate - drug effects</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><issn>1619-7070</issn><issn>1619-7089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpVkc1q3TAQhUVJaX7aB-imiOyVjizbspclNGkgkEWyF7rSOFaQLVeyQvxCfc7oci8tXQwzi3PODPMR8pXDFQeQ3xNA1fQMoCkFPds-kDPe8p5J6PqTv7OEU3Ke0gsA76qu_0ROeVs3wEVzRv48jiGudPA5xGAxvG05OutmpPi2hJQj0jBQ64YBI84rHfOkZ_rsXdh5ndYwaeqLOlE322xKH93zyDy-oqfamDxlr1cX5n3KI1tGnZAa9D7RddQr1a_O-q2YTYhLiHpFyqvmjrlg_7vmM_k4aJ_wy7FfkKebn0_Xv9j9w-3d9Y97Zipeb6xua2h1I602KKUobzBQ210ljJb1IDi3aEFzaGvsdGcF9JybFmUvBpS7RlyQy0PsEsPvjGlVLyHHuWxUJb9tBK-7IuIHkYkhpYiDWqKbdNwUB7Xnog5cVOGi9lzUVjzfjsF5N6H95ziCEO-17Y1o</recordid><startdate>200605</startdate><enddate>200605</enddate><creator>Perillo-Adamer, Florence</creator><creator>Delaloye, Angelika Bischof</creator><creator>Genton, Céline S</creator><creator>Schaffland, Andreas O</creator><creator>Dupertuis, Yves M</creator><creator>Buchegger, Franz</creator><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>200605</creationdate><title>Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine</title><author>Perillo-Adamer, Florence ; 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In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations.
Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment.
The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline.
FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles.</abstract><cop>Germany</cop><pub>Springer Nature B.V</pub><pmid>16450135</pmid><doi>10.1007/s00259-005-0009-y</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1619-7070 |
| ispartof | European journal of nuclear medicine and molecular imaging, 2006-05, Vol.33 (5), p.613-620 |
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| subjects | Cell Cycle - drug effects Cell Cycle - radiation effects Cell Line, Tumor Dose-Response Relationship, Drug Floxuridine - administration & dosage Glioblastoma - metabolism Glioblastoma - pathology Humans Idoxuridine - pharmacokinetics Iodine Radioisotopes - pharmacokinetics Metabolic Clearance Rate - drug effects Radiopharmaceuticals - pharmacokinetics |
| title | Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine |
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