Catabolism of 5-Fluoro-2′-deoxyuridine by Isolated Rat Intestinal Epithelial Cells
Abstract The kinetics of conversion of 5-fluoro-2′-deoxyuridine (FdUrd) to 5-fluorouracil (FUra) by isolated rat intestinal epithelial cells was investigated. Also, the effects of potential inhibitors of this reaction, which is catalyzed by uridine phosphorylase and thymidine phosphorylase, were det...
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| Veröffentlicht in: | Experimental biology and medicine (Maywood, N.J.) N.J.), 1988-12, Vol.189 (3), p.353-361 |
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| container_title | Experimental biology and medicine (Maywood, N.J.) |
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| creator | Lin, Fu-Hsiung Williams, Walter M. |
| description | Abstract
The kinetics of conversion of 5-fluoro-2′-deoxyuridine (FdUrd) to 5-fluorouracil (FUra) by isolated rat intestinal epithelial cells was investigated. Also, the effects of potential inhibitors of this reaction, which is catalyzed by uridine phosphorylase and thymidine phosphorylase, were determined. A 2.5% suspension of isolated cells was incubated with FdUrd or FUra, and at specific times cells were lysed with perchloric acid and fluoropyrimidines were determined by high-performance liquid chromatography. During a 25-min incubation with either FdUrd or FUra, the amount of drug in the incubation system (total volume 0.8 ml) fell by less than 5%. However, in the presence of FdUrd, the amount of FUra increased linearly over 25 min. The apparent V
max and Km
for FUra formation were 17–27 nmole/mg DNA/min and 1.6–2.5 mM, respectively. With each nucleoside phosphorylase inhibitor, the apparent Km
increased but V
max was unaffected. The apparent Ki
values were as follows (in mM): 5-nitrouracil (an inhibitor of both uridine phosphorylase and thymidine phosphorylase), 0.12; 4-thiothymine (a uridine phosphorylase-selective inhibitor), 1.52; and 6-benzyl-2-thiouracil (a thymidine phosphorylase-selective inhibitor), 0.73. It was concluded that intestinal epithelial cells are capable of degrading FdUrd to FUra and that the cells possess both uridine phosphorylase and thymidine phosphorylase activity. |
| doi_str_mv | 10.3181/00379727-189-42818 |
| format | Article |
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The kinetics of conversion of 5-fluoro-2′-deoxyuridine (FdUrd) to 5-fluorouracil (FUra) by isolated rat intestinal epithelial cells was investigated. Also, the effects of potential inhibitors of this reaction, which is catalyzed by uridine phosphorylase and thymidine phosphorylase, were determined. A 2.5% suspension of isolated cells was incubated with FdUrd or FUra, and at specific times cells were lysed with perchloric acid and fluoropyrimidines were determined by high-performance liquid chromatography. During a 25-min incubation with either FdUrd or FUra, the amount of drug in the incubation system (total volume 0.8 ml) fell by less than 5%. However, in the presence of FdUrd, the amount of FUra increased linearly over 25 min. The apparent V
max and Km
for FUra formation were 17–27 nmole/mg DNA/min and 1.6–2.5 mM, respectively. With each nucleoside phosphorylase inhibitor, the apparent Km
increased but V
max was unaffected. The apparent Ki
values were as follows (in mM): 5-nitrouracil (an inhibitor of both uridine phosphorylase and thymidine phosphorylase), 0.12; 4-thiothymine (a uridine phosphorylase-selective inhibitor), 1.52; and 6-benzyl-2-thiouracil (a thymidine phosphorylase-selective inhibitor), 0.73. It was concluded that intestinal epithelial cells are capable of degrading FdUrd to FUra and that the cells possess both uridine phosphorylase and thymidine phosphorylase activity.</description><identifier>ISSN: 0037-9727</identifier><identifier>ISSN: 1535-3702</identifier><identifier>EISSN: 1535-3699</identifier><identifier>EISSN: 1525-1373</identifier><identifier>DOI: 10.3181/00379727-189-42818</identifier><identifier>PMID: 2974595</identifier><identifier>CODEN: PSEBAA</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Biological and medical sciences ; Epithelium - metabolism ; Floxuridine - metabolism ; Fluorouracil - metabolism ; Fundamental and applied biological sciences. Psychology ; In Vitro Techniques ; Intestinal Mucosa - metabolism ; Intestine. Mesentery ; Kinetics ; Male ; Pentosyltransferases - antagonists & inhibitors ; Pyrimidine Phosphorylases ; Rats ; Rats, Inbred Strains ; Thymidine - analogs & derivatives ; Thymidine - pharmacology ; Uracil - analogs & derivatives ; Uracil - pharmacology ; Vertebrates: digestive system</subject><ispartof>Experimental biology and medicine (Maywood, N.J.), 1988-12, Vol.189 (3), p.353-361</ispartof><rights>1990 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c367t-6096595c63264442a1177e435c02b3150924cee4901372ef3791ab4cd02a42063</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6775725$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2974595$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Fu-Hsiung</creatorcontrib><creatorcontrib>Williams, Walter M.</creatorcontrib><title>Catabolism of 5-Fluoro-2′-deoxyuridine by Isolated Rat Intestinal Epithelial Cells</title><title>Experimental biology and medicine (Maywood, N.J.)</title><addtitle>Proc Soc Exp Biol Med</addtitle><description>Abstract
The kinetics of conversion of 5-fluoro-2′-deoxyuridine (FdUrd) to 5-fluorouracil (FUra) by isolated rat intestinal epithelial cells was investigated. Also, the effects of potential inhibitors of this reaction, which is catalyzed by uridine phosphorylase and thymidine phosphorylase, were determined. A 2.5% suspension of isolated cells was incubated with FdUrd or FUra, and at specific times cells were lysed with perchloric acid and fluoropyrimidines were determined by high-performance liquid chromatography. During a 25-min incubation with either FdUrd or FUra, the amount of drug in the incubation system (total volume 0.8 ml) fell by less than 5%. However, in the presence of FdUrd, the amount of FUra increased linearly over 25 min. The apparent V
max and Km
for FUra formation were 17–27 nmole/mg DNA/min and 1.6–2.5 mM, respectively. With each nucleoside phosphorylase inhibitor, the apparent Km
increased but V
max was unaffected. The apparent Ki
values were as follows (in mM): 5-nitrouracil (an inhibitor of both uridine phosphorylase and thymidine phosphorylase), 0.12; 4-thiothymine (a uridine phosphorylase-selective inhibitor), 1.52; and 6-benzyl-2-thiouracil (a thymidine phosphorylase-selective inhibitor), 0.73. It was concluded that intestinal epithelial cells are capable of degrading FdUrd to FUra and that the cells possess both uridine phosphorylase and thymidine phosphorylase activity.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Epithelium - metabolism</subject><subject>Floxuridine - metabolism</subject><subject>Fluorouracil - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>In Vitro Techniques</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestine. Mesentery</subject><subject>Kinetics</subject><subject>Male</subject><subject>Pentosyltransferases - antagonists & inhibitors</subject><subject>Pyrimidine Phosphorylases</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Thymidine - analogs & derivatives</subject><subject>Thymidine - pharmacology</subject><subject>Uracil - analogs & derivatives</subject><subject>Uracil - pharmacology</subject><subject>Vertebrates: digestive system</subject><issn>0037-9727</issn><issn>1535-3702</issn><issn>1535-3699</issn><issn>1525-1373</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKAzEUhoMoWi8vIAizEHfR3DNZSvFSEATRdchkMhpJJzWZAbvzmXwkn8TUVpeuEjjf-fPnA-AYo3OKa3yBEJVKEglxrSAjNa63wARzyiEVSm2DyQqAK2IP7Of8ihDmkohdsEuUZFzxCXicmsE0Mfg8r2JXcXgdxpgiJF8fn7B18X05Jt_63lXNsprlGMzg2urBDNWsH1wefG9CdbXww4sLvlynLoR8CHY6E7I72pwH4On66nF6C-_ub2bTyztoqZADFEiJUsIKSgRjjBiMpXSMcotIQzFHijDrHFMIU0lcVz6LTcNsi4hhBAl6AM7WuYsU38bSRs99tqWB6V0cs5Z1iaecFJCsQZtizsl1epH83KSlxkivVOpflbqo1D8qy9LJJn1s5q79W9m4K_PTzdxka0KXTG99_sOElEX2CrtYY9k8O_0ax1SU5f8e_gZVn4fM</recordid><startdate>19881201</startdate><enddate>19881201</enddate><creator>Lin, Fu-Hsiung</creator><creator>Williams, Walter M.</creator><general>SAGE Publications</general><general>Blackwell Science</general><scope>IQODW</scope><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></search><sort><creationdate>19881201</creationdate><title>Catabolism of 5-Fluoro-2′-deoxyuridine by Isolated Rat Intestinal Epithelial Cells</title><author>Lin, Fu-Hsiung ; Williams, Walter M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-6096595c63264442a1177e435c02b3150924cee4901372ef3791ab4cd02a42063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Epithelium - metabolism</topic><topic>Floxuridine - metabolism</topic><topic>Fluorouracil - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>In Vitro Techniques</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestine. Mesentery</topic><topic>Kinetics</topic><topic>Male</topic><topic>Pentosyltransferases - antagonists & inhibitors</topic><topic>Pyrimidine Phosphorylases</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Thymidine - analogs & derivatives</topic><topic>Thymidine - pharmacology</topic><topic>Uracil - analogs & derivatives</topic><topic>Uracil - pharmacology</topic><topic>Vertebrates: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Fu-Hsiung</creatorcontrib><creatorcontrib>Williams, Walter M.</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Experimental biology and medicine (Maywood, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Fu-Hsiung</au><au>Williams, Walter M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Catabolism of 5-Fluoro-2′-deoxyuridine by Isolated Rat Intestinal Epithelial Cells</atitle><jtitle>Experimental biology and medicine (Maywood, N.J.)</jtitle><addtitle>Proc Soc Exp Biol Med</addtitle><date>1988-12-01</date><risdate>1988</risdate><volume>189</volume><issue>3</issue><spage>353</spage><epage>361</epage><pages>353-361</pages><issn>0037-9727</issn><issn>1535-3702</issn><eissn>1535-3699</eissn><eissn>1525-1373</eissn><coden>PSEBAA</coden><abstract>Abstract
The kinetics of conversion of 5-fluoro-2′-deoxyuridine (FdUrd) to 5-fluorouracil (FUra) by isolated rat intestinal epithelial cells was investigated. Also, the effects of potential inhibitors of this reaction, which is catalyzed by uridine phosphorylase and thymidine phosphorylase, were determined. A 2.5% suspension of isolated cells was incubated with FdUrd or FUra, and at specific times cells were lysed with perchloric acid and fluoropyrimidines were determined by high-performance liquid chromatography. During a 25-min incubation with either FdUrd or FUra, the amount of drug in the incubation system (total volume 0.8 ml) fell by less than 5%. However, in the presence of FdUrd, the amount of FUra increased linearly over 25 min. The apparent V
max and Km
for FUra formation were 17–27 nmole/mg DNA/min and 1.6–2.5 mM, respectively. With each nucleoside phosphorylase inhibitor, the apparent Km
increased but V
max was unaffected. The apparent Ki
values were as follows (in mM): 5-nitrouracil (an inhibitor of both uridine phosphorylase and thymidine phosphorylase), 0.12; 4-thiothymine (a uridine phosphorylase-selective inhibitor), 1.52; and 6-benzyl-2-thiouracil (a thymidine phosphorylase-selective inhibitor), 0.73. It was concluded that intestinal epithelial cells are capable of degrading FdUrd to FUra and that the cells possess both uridine phosphorylase and thymidine phosphorylase activity.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>2974595</pmid><doi>10.3181/00379727-189-42818</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Experimental biology and medicine (Maywood, N.J.), 1988-12, Vol.189 (3), p.353-361 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Epithelium - metabolism Floxuridine - metabolism Fluorouracil - metabolism Fundamental and applied biological sciences. Psychology In Vitro Techniques Intestinal Mucosa - metabolism Intestine. Mesentery Kinetics Male Pentosyltransferases - antagonists & inhibitors Pyrimidine Phosphorylases Rats Rats, Inbred Strains Thymidine - analogs & derivatives Thymidine - pharmacology Uracil - analogs & derivatives Uracil - pharmacology Vertebrates: digestive system |
| title | Catabolism of 5-Fluoro-2′-deoxyuridine by Isolated Rat Intestinal Epithelial Cells |
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