Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemia
The glutamine antagonists, acivicin (NSC 163501), azaserine (NSC 742), and 6-diazo-5-oxo-L-norleucine (DON) (NSC 7365), are potent inhibitors of many glutamine-dependent amidotransferases in vitro. Experiments performed with mouse L1210 leukemia growing in culture show that each antagonist has diffe...
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Veröffentlicht in: | The Journal of biological chemistry 1990-07, Vol.265 (19), p.11377-11381 |
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creator | LYONS, S. D SANT, M. E CHRISTOPHERSON, R. I |
description | The glutamine antagonists, acivicin (NSC 163501), azaserine (NSC 742), and 6-diazo-5-oxo-L-norleucine (DON) (NSC 7365), are
potent inhibitors of many glutamine-dependent amidotransferases in vitro. Experiments performed with mouse L1210 leukemia
growing in culture show that each antagonist has different sites of inhibition in nucleotide biosynthesis. Acivicin is a potent
inhibitor of CTP and GMP synthetases and partially inhibits N-formylglycineamidine ribotide (FGAM) synthetase of purine biosynthesis.
DON inhibits FGAM synthetase, CTP synthetase, and glucosamine-6-phosphate isomerase. Azaserine inhibits FGAM synthetase and
glucosamine-6-phosphate isomerase. Large accumulations of FGAR and its di- and triphosphate derivatives were observed for
all three antagonists which could interfere with the biosynthesis of nucleic acids, providing another mechanism of cytotoxicity.
Acivicin, azaserine, and DON are not potent inhibitors of carbamyl phosphate synthetase II (glutamine-hydrolyzing) and amidophosphoribosyltransferase
in leukemia cells growing in culture although there are reports of such inhibitions in vitro. Blockade of de novo purine biosynthesis
by these three antagonists results in a "complementary stimulation" of de novo pyrimidine biosynthesis. |
doi_str_mv | 10.1016/S0021-9258(19)38603-X |
format | Article |
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potent inhibitors of many glutamine-dependent amidotransferases in vitro. Experiments performed with mouse L1210 leukemia
growing in culture show that each antagonist has different sites of inhibition in nucleotide biosynthesis. Acivicin is a potent
inhibitor of CTP and GMP synthetases and partially inhibits N-formylglycineamidine ribotide (FGAM) synthetase of purine biosynthesis.
DON inhibits FGAM synthetase, CTP synthetase, and glucosamine-6-phosphate isomerase. Azaserine inhibits FGAM synthetase and
glucosamine-6-phosphate isomerase. Large accumulations of FGAR and its di- and triphosphate derivatives were observed for
all three antagonists which could interfere with the biosynthesis of nucleic acids, providing another mechanism of cytotoxicity.
Acivicin, azaserine, and DON are not potent inhibitors of carbamyl phosphate synthetase II (glutamine-hydrolyzing) and amidophosphoribosyltransferase
in leukemia cells growing in culture although there are reports of such inhibitions in vitro. Blockade of de novo purine biosynthesis
by these three antagonists results in a "complementary stimulation" of de novo pyrimidine biosynthesis.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(19)38603-X</identifier><identifier>PMID: 2358467</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>6-diazo-5-oxo-L-norleucine ; Animals ; azaserine ; Azaserine - pharmacology ; Azo Compounds - pharmacology ; Biological and medical sciences ; Carbon-Nitrogen Ligases ; Cell Line ; Cell physiology ; Chromatography, High Pressure Liquid ; Diazooxonorleucine - pharmacology ; Fundamental and applied biological sciences. Psychology ; glutamine ; Glutamine - antagonists & inhibitors ; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - antagonists & inhibitors ; Isoxazoles - pharmacology ; Leukemia L1210 - enzymology ; Ligases - antagonists & inhibitors ; Mice ; Molecular and cellular biology ; Nucleotides - biosynthesis ; Oxazoles - pharmacology ; Responses to growth factors, tumor promotors, other factors ; Spectrophotometry, Ultraviolet</subject><ispartof>The Journal of biological chemistry, 1990-07, Vol.265 (19), p.11377-11381</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-b2eb6924fb80fbece9506d10845af084b04a739a4ee5df2b36aec7e1282898643</citedby><cites>FETCH-LOGICAL-c493t-b2eb6924fb80fbece9506d10845af084b04a739a4ee5df2b36aec7e1282898643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19738044$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2358467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LYONS, S. D</creatorcontrib><creatorcontrib>SANT, M. E</creatorcontrib><creatorcontrib>CHRISTOPHERSON, R. I</creatorcontrib><title>Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemia</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The glutamine antagonists, acivicin (NSC 163501), azaserine (NSC 742), and 6-diazo-5-oxo-L-norleucine (DON) (NSC 7365), are
potent inhibitors of many glutamine-dependent amidotransferases in vitro. Experiments performed with mouse L1210 leukemia
growing in culture show that each antagonist has different sites of inhibition in nucleotide biosynthesis. Acivicin is a potent
inhibitor of CTP and GMP synthetases and partially inhibits N-formylglycineamidine ribotide (FGAM) synthetase of purine biosynthesis.
DON inhibits FGAM synthetase, CTP synthetase, and glucosamine-6-phosphate isomerase. Azaserine inhibits FGAM synthetase and
glucosamine-6-phosphate isomerase. Large accumulations of FGAR and its di- and triphosphate derivatives were observed for
all three antagonists which could interfere with the biosynthesis of nucleic acids, providing another mechanism of cytotoxicity.
Acivicin, azaserine, and DON are not potent inhibitors of carbamyl phosphate synthetase II (glutamine-hydrolyzing) and amidophosphoribosyltransferase
in leukemia cells growing in culture although there are reports of such inhibitions in vitro. Blockade of de novo purine biosynthesis
by these three antagonists results in a "complementary stimulation" of de novo pyrimidine biosynthesis.</description><subject>6-diazo-5-oxo-L-norleucine</subject><subject>Animals</subject><subject>azaserine</subject><subject>Azaserine - pharmacology</subject><subject>Azo Compounds - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Carbon-Nitrogen Ligases</subject><subject>Cell Line</subject><subject>Cell physiology</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Diazooxonorleucine - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>glutamine</subject><subject>Glutamine - antagonists & inhibitors</subject><subject>Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - antagonists & inhibitors</subject><subject>Isoxazoles - pharmacology</subject><subject>Leukemia L1210 - enzymology</subject><subject>Ligases - antagonists & inhibitors</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Nucleotides - biosynthesis</subject><subject>Oxazoles - pharmacology</subject><subject>Responses to growth factors, tumor promotors, other factors</subject><subject>Spectrophotometry, Ultraviolet</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtOwzAQRS0EKqXwCZWyAASLgN-xl6gqD6kSC0DqznLcSWuIE4gTQf-e9CGYxczi3pm5OgiNCb4hmMjbF4wpSTUV6oroa6YkZun8AA0JVixlgswP0fDPcoxOYnzHfXFNBmhAmVBcZkM0nazbuq1_vEsCuJWtfAwxqYtkWXatDb6CxFatXda90MbEV0mouwjJjFCCkxK6DwjenqKjwpYRzvZzhN7up6-Tx3T2_PA0uZuljmvWpjmFXGrKi1zhIgcHWmC56ANzYYu-55jbjGnLAcSioDmTFlwGhCqqtJKcjdDl7u5nU391EFsTfHRQlraCPpYhQmrMM9Ebxc7omjrGBgrz2fhgm7Uh2GzwmS0-s2FjiDZbfGbe7433D7o8wOJva8-r1y_2uo3OlkVjK-fj_3GdMYX5Juj5zrfyy9W3b8DkvnYrCIZKsXlICMsy9gsFZIOC</recordid><startdate>19900705</startdate><enddate>19900705</enddate><creator>LYONS, S. D</creator><creator>SANT, M. E</creator><creator>CHRISTOPHERSON, R. I</creator><general>American Society for Biochemistry and Molecular Biology</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>7QL</scope><scope>C1K</scope></search><sort><creationdate>19900705</creationdate><title>Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemia</title><author>LYONS, S. D ; SANT, M. E ; CHRISTOPHERSON, R. I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-b2eb6924fb80fbece9506d10845af084b04a739a4ee5df2b36aec7e1282898643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>6-diazo-5-oxo-L-norleucine</topic><topic>Animals</topic><topic>azaserine</topic><topic>Azaserine - pharmacology</topic><topic>Azo Compounds - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Carbon-Nitrogen Ligases</topic><topic>Cell Line</topic><topic>Cell physiology</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Diazooxonorleucine - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>glutamine</topic><topic>Glutamine - antagonists & inhibitors</topic><topic>Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - antagonists & inhibitors</topic><topic>Isoxazoles - pharmacology</topic><topic>Leukemia L1210 - enzymology</topic><topic>Ligases - antagonists & inhibitors</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Nucleotides - biosynthesis</topic><topic>Oxazoles - pharmacology</topic><topic>Responses to growth factors, tumor promotors, other factors</topic><topic>Spectrophotometry, Ultraviolet</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LYONS, S. D</creatorcontrib><creatorcontrib>SANT, M. E</creatorcontrib><creatorcontrib>CHRISTOPHERSON, R. I</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LYONS, S. D</au><au>SANT, M. E</au><au>CHRISTOPHERSON, R. I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemia</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1990-07-05</date><risdate>1990</risdate><volume>265</volume><issue>19</issue><spage>11377</spage><epage>11381</epage><pages>11377-11381</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>The glutamine antagonists, acivicin (NSC 163501), azaserine (NSC 742), and 6-diazo-5-oxo-L-norleucine (DON) (NSC 7365), are
potent inhibitors of many glutamine-dependent amidotransferases in vitro. Experiments performed with mouse L1210 leukemia
growing in culture show that each antagonist has different sites of inhibition in nucleotide biosynthesis. Acivicin is a potent
inhibitor of CTP and GMP synthetases and partially inhibits N-formylglycineamidine ribotide (FGAM) synthetase of purine biosynthesis.
DON inhibits FGAM synthetase, CTP synthetase, and glucosamine-6-phosphate isomerase. Azaserine inhibits FGAM synthetase and
glucosamine-6-phosphate isomerase. Large accumulations of FGAR and its di- and triphosphate derivatives were observed for
all three antagonists which could interfere with the biosynthesis of nucleic acids, providing another mechanism of cytotoxicity.
Acivicin, azaserine, and DON are not potent inhibitors of carbamyl phosphate synthetase II (glutamine-hydrolyzing) and amidophosphoribosyltransferase
in leukemia cells growing in culture although there are reports of such inhibitions in vitro. Blockade of de novo purine biosynthesis
by these three antagonists results in a "complementary stimulation" of de novo pyrimidine biosynthesis.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>2358467</pmid><doi>10.1016/S0021-9258(19)38603-X</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 6-diazo-5-oxo-L-norleucine Animals azaserine Azaserine - pharmacology Azo Compounds - pharmacology Biological and medical sciences Carbon-Nitrogen Ligases Cell Line Cell physiology Chromatography, High Pressure Liquid Diazooxonorleucine - pharmacology Fundamental and applied biological sciences. Psychology glutamine Glutamine - antagonists & inhibitors Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - antagonists & inhibitors Isoxazoles - pharmacology Leukemia L1210 - enzymology Ligases - antagonists & inhibitors Mice Molecular and cellular biology Nucleotides - biosynthesis Oxazoles - pharmacology Responses to growth factors, tumor promotors, other factors Spectrophotometry, Ultraviolet |
title | Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemia |
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