Mechanism of Growth Inhibition by 5-Fluorouracil. Reversal Studies with Pyrimidine Metabolites in Vitro
Summary Continuous exposure to FU at a concentration of 0.05 μg/ml was uniformly toxic for a tissue culture strain of Ehrlich ascites tumor, ELD. Of the normal pyrimidine metabolites tested in the presence of FU, neither U, UR, or OA exerted a protective effect against FU toxicity. However, TdR did...
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Veröffentlicht in: | Experimental biology and medicine (Maywood, N.J.) N.J.), 1969-07, Vol.131 (3), p.1068-1072 |
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container_title | Experimental biology and medicine (Maywood, N.J.) |
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creator | Reeves, William J. Cailleau, Relda |
description | Summary
Continuous exposure to FU at a concentration of 0.05 μg/ml was uniformly toxic for a tissue culture strain of Ehrlich ascites tumor, ELD. Of the normal pyrimidine metabolites tested in the presence of FU, neither U, UR, or OA exerted a protective effect against FU toxicity. However, TdR did have a protective effect at a concentration of 5 μg/ml, permitting normal growth of ELD cells. At higher FU concentrations, TdR had less protective action. Brief (1-3 hr) exposures to FU at high concentrations (5-50 μg ml) produced toxicity which could be counteracted when the FU exposure was followed by cell washing and continuous exposure to TdR. These findings suggest that TdRP formation is the step most sensitive to FU. |
doi_str_mv | 10.3181/00379727-131-34041 |
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Continuous exposure to FU at a concentration of 0.05 μg/ml was uniformly toxic for a tissue culture strain of Ehrlich ascites tumor, ELD. Of the normal pyrimidine metabolites tested in the presence of FU, neither U, UR, or OA exerted a protective effect against FU toxicity. However, TdR did have a protective effect at a concentration of 5 μg/ml, permitting normal growth of ELD cells. At higher FU concentrations, TdR had less protective action. Brief (1-3 hr) exposures to FU at high concentrations (5-50 μg ml) produced toxicity which could be counteracted when the FU exposure was followed by cell washing and continuous exposure to TdR. These findings suggest that TdRP formation is the step most sensitive to FU.</description><identifier>ISSN: 0037-9727</identifier><identifier>ISSN: 1535-3702</identifier><identifier>EISSN: 1535-3699</identifier><identifier>DOI: 10.3181/00379727-131-34041</identifier><identifier>PMID: 5791777</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Carcinoma, Ehrlich Tumor - metabolism ; Culture Techniques ; Depression, Chemical ; DNA, Neoplasm - biosynthesis ; Fluorouracil - toxicity ; Mice ; Nucleotides - biosynthesis ; Orotic Acid - pharmacology ; RNA, Neoplasm - biosynthesis ; Thymidine - pharmacology ; Uridine - pharmacology</subject><ispartof>Experimental biology and medicine (Maywood, N.J.), 1969-07, Vol.131 (3), p.1068-1072</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c338t-d7b20485d2135f6b2ca2a142105f2e27571cef57ed2c2933ca89da4012df56cb3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/5791777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reeves, William J.</creatorcontrib><creatorcontrib>Cailleau, Relda</creatorcontrib><title>Mechanism of Growth Inhibition by 5-Fluorouracil. Reversal Studies with Pyrimidine Metabolites in Vitro</title><title>Experimental biology and medicine (Maywood, N.J.)</title><addtitle>Proc Soc Exp Biol Med</addtitle><description>Summary
Continuous exposure to FU at a concentration of 0.05 μg/ml was uniformly toxic for a tissue culture strain of Ehrlich ascites tumor, ELD. Of the normal pyrimidine metabolites tested in the presence of FU, neither U, UR, or OA exerted a protective effect against FU toxicity. However, TdR did have a protective effect at a concentration of 5 μg/ml, permitting normal growth of ELD cells. At higher FU concentrations, TdR had less protective action. Brief (1-3 hr) exposures to FU at high concentrations (5-50 μg ml) produced toxicity which could be counteracted when the FU exposure was followed by cell washing and continuous exposure to TdR. These findings suggest that TdRP formation is the step most sensitive to FU.</description><subject>Animals</subject><subject>Carcinoma, Ehrlich Tumor - metabolism</subject><subject>Culture Techniques</subject><subject>Depression, Chemical</subject><subject>DNA, Neoplasm - biosynthesis</subject><subject>Fluorouracil - toxicity</subject><subject>Mice</subject><subject>Nucleotides - biosynthesis</subject><subject>Orotic Acid - pharmacology</subject><subject>RNA, Neoplasm - biosynthesis</subject><subject>Thymidine - pharmacology</subject><subject>Uridine - pharmacology</subject><issn>0037-9727</issn><issn>1535-3702</issn><issn>1535-3699</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1969</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1PwjAUhhujQUT_gIlJ_0ChH-u6XRoiSALR-HW7dG0HJWMl7Qbh31sEvfTqXLzneXPOA8A9wUNGMjLCmIlcUIEII4glOCEXoE8444ileX4J-scFdNy4BjchrDEmXNC0B3pc5EQI0QfLhVEr2diwga6CU-_27QrOmpUtbWtdA8sD5GhSd867zktl6yF8Mzvjg6zhe9tpawLc28i8HrzdWG0bAxemlaWrbRsz28Av23p3C64qWQdzd54D8Dl5-hg_o_nLdDZ-nCPFWNYiLUqKk4xrShiv0pIqSSVJKMG8ooYKLogyFRdGU0VzxpTMci0TTKiueKpKNgD01Ku8C8GbqtjGu6Q_FAQXR2nFr7QiSit-pEXo4QRtu3Jj9B9ythTz0SkPcmmKdTTRxB_-a_wGRTN15A</recordid><startdate>196907</startdate><enddate>196907</enddate><creator>Reeves, William J.</creator><creator>Cailleau, Relda</creator><general>SAGE Publications</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></search><sort><creationdate>196907</creationdate><title>Mechanism of Growth Inhibition by 5-Fluorouracil. Reversal Studies with Pyrimidine Metabolites in Vitro</title><author>Reeves, William J. ; Cailleau, Relda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c338t-d7b20485d2135f6b2ca2a142105f2e27571cef57ed2c2933ca89da4012df56cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1969</creationdate><topic>Animals</topic><topic>Carcinoma, Ehrlich Tumor - metabolism</topic><topic>Culture Techniques</topic><topic>Depression, Chemical</topic><topic>DNA, Neoplasm - biosynthesis</topic><topic>Fluorouracil - toxicity</topic><topic>Mice</topic><topic>Nucleotides - biosynthesis</topic><topic>Orotic Acid - pharmacology</topic><topic>RNA, Neoplasm - biosynthesis</topic><topic>Thymidine - pharmacology</topic><topic>Uridine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reeves, William J.</creatorcontrib><creatorcontrib>Cailleau, Relda</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Experimental biology and medicine (Maywood, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reeves, William J.</au><au>Cailleau, Relda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanism of Growth Inhibition by 5-Fluorouracil. Reversal Studies with Pyrimidine Metabolites in Vitro</atitle><jtitle>Experimental biology and medicine (Maywood, N.J.)</jtitle><addtitle>Proc Soc Exp Biol Med</addtitle><date>1969-07</date><risdate>1969</risdate><volume>131</volume><issue>3</issue><spage>1068</spage><epage>1072</epage><pages>1068-1072</pages><issn>0037-9727</issn><issn>1535-3702</issn><eissn>1535-3699</eissn><abstract>Summary
Continuous exposure to FU at a concentration of 0.05 μg/ml was uniformly toxic for a tissue culture strain of Ehrlich ascites tumor, ELD. Of the normal pyrimidine metabolites tested in the presence of FU, neither U, UR, or OA exerted a protective effect against FU toxicity. However, TdR did have a protective effect at a concentration of 5 μg/ml, permitting normal growth of ELD cells. At higher FU concentrations, TdR had less protective action. Brief (1-3 hr) exposures to FU at high concentrations (5-50 μg ml) produced toxicity which could be counteracted when the FU exposure was followed by cell washing and continuous exposure to TdR. These findings suggest that TdRP formation is the step most sensitive to FU.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>5791777</pmid><doi>10.3181/00379727-131-34041</doi><tpages>5</tpages></addata></record> |
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subjects | Animals Carcinoma, Ehrlich Tumor - metabolism Culture Techniques Depression, Chemical DNA, Neoplasm - biosynthesis Fluorouracil - toxicity Mice Nucleotides - biosynthesis Orotic Acid - pharmacology RNA, Neoplasm - biosynthesis Thymidine - pharmacology Uridine - pharmacology |
title | Mechanism of Growth Inhibition by 5-Fluorouracil. Reversal Studies with Pyrimidine Metabolites in Vitro |
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