The intracellular content of dihydrofolate reductase: possibilities for control and implications for chemotherapy
Intracellular levels of DHFR can be modulated by mechanisms other than gene amplification. We found that MTX itself has an effect and the important features of this mechanism are as follows: (a) Sub-saturating doses of MTX induce intracellular DHFR activity by increasing DHFR synthesis; (b) The time...
Gespeichert in:
| Veröffentlicht in: | Advances in enzyme regulation 1984, Vol.22, p.15-26 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 26 |
|---|---|
| container_issue | |
| container_start_page | 15 |
| container_title | Advances in enzyme regulation |
| container_volume | 22 |
| creator | Bastow, K.F. Prabhu, R. Cheng, Y-C. |
| description | Intracellular levels of DHFR can be modulated by mechanisms other than gene amplification. We found that MTX itself has an effect and the important features of this mechanism are as follows: (a) Sub-saturating doses of MTX induce intracellular DHFR activity by increasing DHFR synthesis; (b) The time-dependent effect seems quite specific for DHFR and is reversible (7); (c) Elevated DHFR synthesis is accompanied by disproportionate increases in DHFR mRNA; (d) The time scale for maximum induction is appreciably longer than the cell generation time. We suggest that part of the control involved is translational and we postulate that DHFR may regulate its own biosynthesis through feedback mechanisms. It is conceivable that the induction phenomenon could affect the clinical efficacy of MTX-therapy in some instances. |
| doi_str_mv | 10.1016/0065-2571(84)90006-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_81225035</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>0065257184900062</els_id><sourcerecordid>81225035</sourcerecordid><originalsourceid>FETCH-LOGICAL-c357t-7bae3ab80fcf5ad702710a89c0506c8744f3cc67ab3a18d2f77ccbe31726c0c73</originalsourceid><addsrcrecordid>eNp9kE9LJDEQxcOyMo6630AhJ1kPrfnT3Wk9CIu4u4LgZTyHdKXCRLo7PUl6Yb69Pc4wxz0VxXuvivcj5JKzW854fcdYXRWiUvxnU97cs3ktxDey5I2ShSil-k6WR8spOUvpgzEuVK0WZFGXqqpLtiSb1RqpH3I0gF03dSZSCEPGIdPgqPXrrY3Bhc5kpBHtBNkkfKBjSMm3vvPZY6Iu7FMxdNQMlvp-7DyY7MNwENfYh7zGaMbtBTlxpkv44zDPyfvv59XT3-L17c_L06_XAmSlcqFag9K0DXPgKmMVE4oz09wDq1gNjSpLJwFqZVppeGOFUwqgRcmVqIGBkufken93jGEzYcq692lX0gwYpqQbLkTFZDUby70R4twqotNj9L2JW82Z3pHWO4x6h1E3pf4ircUcuzrcn9oe7TF0QDvrj3sd55L_PEadwOMAaH1EyNoG__8Hn1YqkD0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>81225035</pqid></control><display><type>article</type><title>The intracellular content of dihydrofolate reductase: possibilities for control and implications for chemotherapy</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Bastow, K.F. ; Prabhu, R. ; Cheng, Y-C.</creator><creatorcontrib>Bastow, K.F. ; Prabhu, R. ; Cheng, Y-C.</creatorcontrib><description>Intracellular levels of DHFR can be modulated by mechanisms other than gene amplification. We found that MTX itself has an effect and the important features of this mechanism are as follows: (a) Sub-saturating doses of MTX induce intracellular DHFR activity by increasing DHFR synthesis; (b) The time-dependent effect seems quite specific for DHFR and is reversible (7); (c) Elevated DHFR synthesis is accompanied by disproportionate increases in DHFR mRNA; (d) The time scale for maximum induction is appreciably longer than the cell generation time. We suggest that part of the control involved is translational and we postulate that DHFR may regulate its own biosynthesis through feedback mechanisms. It is conceivable that the induction phenomenon could affect the clinical efficacy of MTX-therapy in some instances.</description><identifier>ISSN: 0065-2571</identifier><identifier>EISSN: 1873-2437</identifier><identifier>DOI: 10.1016/0065-2571(84)90006-2</identifier><identifier>PMID: 6475640</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Cell Line ; Clone Cells ; Drug Resistance ; Enzyme Induction - drug effects ; Humans ; Intracellular Fluid - drug effects ; Intracellular Fluid - enzymology ; Methotrexate - pharmacology ; RNA, Messenger - metabolism ; Tetrahydrofolate Dehydrogenase - biosynthesis ; Tetrahydrofolate Dehydrogenase - genetics ; Time Factors</subject><ispartof>Advances in enzyme regulation, 1984, Vol.22, p.15-26</ispartof><rights>1984</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-7bae3ab80fcf5ad702710a89c0506c8744f3cc67ab3a18d2f77ccbe31726c0c73</citedby><cites>FETCH-LOGICAL-c357t-7bae3ab80fcf5ad702710a89c0506c8744f3cc67ab3a18d2f77ccbe31726c0c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0065-2571(84)90006-2$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6475640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bastow, K.F.</creatorcontrib><creatorcontrib>Prabhu, R.</creatorcontrib><creatorcontrib>Cheng, Y-C.</creatorcontrib><title>The intracellular content of dihydrofolate reductase: possibilities for control and implications for chemotherapy</title><title>Advances in enzyme regulation</title><addtitle>Adv Enzyme Regul</addtitle><description>Intracellular levels of DHFR can be modulated by mechanisms other than gene amplification. We found that MTX itself has an effect and the important features of this mechanism are as follows: (a) Sub-saturating doses of MTX induce intracellular DHFR activity by increasing DHFR synthesis; (b) The time-dependent effect seems quite specific for DHFR and is reversible (7); (c) Elevated DHFR synthesis is accompanied by disproportionate increases in DHFR mRNA; (d) The time scale for maximum induction is appreciably longer than the cell generation time. We suggest that part of the control involved is translational and we postulate that DHFR may regulate its own biosynthesis through feedback mechanisms. It is conceivable that the induction phenomenon could affect the clinical efficacy of MTX-therapy in some instances.</description><subject>Cell Line</subject><subject>Clone Cells</subject><subject>Drug Resistance</subject><subject>Enzyme Induction - drug effects</subject><subject>Humans</subject><subject>Intracellular Fluid - drug effects</subject><subject>Intracellular Fluid - enzymology</subject><subject>Methotrexate - pharmacology</subject><subject>RNA, Messenger - metabolism</subject><subject>Tetrahydrofolate Dehydrogenase - biosynthesis</subject><subject>Tetrahydrofolate Dehydrogenase - genetics</subject><subject>Time Factors</subject><issn>0065-2571</issn><issn>1873-2437</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1984</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9LJDEQxcOyMo6630AhJ1kPrfnT3Wk9CIu4u4LgZTyHdKXCRLo7PUl6Yb69Pc4wxz0VxXuvivcj5JKzW854fcdYXRWiUvxnU97cs3ktxDey5I2ShSil-k6WR8spOUvpgzEuVK0WZFGXqqpLtiSb1RqpH3I0gF03dSZSCEPGIdPgqPXrrY3Bhc5kpBHtBNkkfKBjSMm3vvPZY6Iu7FMxdNQMlvp-7DyY7MNwENfYh7zGaMbtBTlxpkv44zDPyfvv59XT3-L17c_L06_XAmSlcqFag9K0DXPgKmMVE4oz09wDq1gNjSpLJwFqZVppeGOFUwqgRcmVqIGBkufken93jGEzYcq692lX0gwYpqQbLkTFZDUby70R4twqotNj9L2JW82Z3pHWO4x6h1E3pf4ircUcuzrcn9oe7TF0QDvrj3sd55L_PEadwOMAaH1EyNoG__8Hn1YqkD0</recordid><startdate>1984</startdate><enddate>1984</enddate><creator>Bastow, K.F.</creator><creator>Prabhu, R.</creator><creator>Cheng, Y-C.</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>1984</creationdate><title>The intracellular content of dihydrofolate reductase: possibilities for control and implications for chemotherapy</title><author>Bastow, K.F. ; Prabhu, R. ; Cheng, Y-C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-7bae3ab80fcf5ad702710a89c0506c8744f3cc67ab3a18d2f77ccbe31726c0c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1984</creationdate><topic>Cell Line</topic><topic>Clone Cells</topic><topic>Drug Resistance</topic><topic>Enzyme Induction - drug effects</topic><topic>Humans</topic><topic>Intracellular Fluid - drug effects</topic><topic>Intracellular Fluid - enzymology</topic><topic>Methotrexate - pharmacology</topic><topic>RNA, Messenger - metabolism</topic><topic>Tetrahydrofolate Dehydrogenase - biosynthesis</topic><topic>Tetrahydrofolate Dehydrogenase - genetics</topic><topic>Time Factors</topic><toplevel>online_resources</toplevel><creatorcontrib>Bastow, K.F.</creatorcontrib><creatorcontrib>Prabhu, R.</creatorcontrib><creatorcontrib>Cheng, Y-C.</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><jtitle>Advances in enzyme regulation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bastow, K.F.</au><au>Prabhu, R.</au><au>Cheng, Y-C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The intracellular content of dihydrofolate reductase: possibilities for control and implications for chemotherapy</atitle><jtitle>Advances in enzyme regulation</jtitle><addtitle>Adv Enzyme Regul</addtitle><date>1984</date><risdate>1984</risdate><volume>22</volume><spage>15</spage><epage>26</epage><pages>15-26</pages><issn>0065-2571</issn><eissn>1873-2437</eissn><abstract>Intracellular levels of DHFR can be modulated by mechanisms other than gene amplification. We found that MTX itself has an effect and the important features of this mechanism are as follows: (a) Sub-saturating doses of MTX induce intracellular DHFR activity by increasing DHFR synthesis; (b) The time-dependent effect seems quite specific for DHFR and is reversible (7); (c) Elevated DHFR synthesis is accompanied by disproportionate increases in DHFR mRNA; (d) The time scale for maximum induction is appreciably longer than the cell generation time. We suggest that part of the control involved is translational and we postulate that DHFR may regulate its own biosynthesis through feedback mechanisms. It is conceivable that the induction phenomenon could affect the clinical efficacy of MTX-therapy in some instances.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>6475640</pmid><doi>10.1016/0065-2571(84)90006-2</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0065-2571 |
| ispartof | Advances in enzyme regulation, 1984, Vol.22, p.15-26 |
| issn | 0065-2571 1873-2437 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_81225035 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Cell Line Clone Cells Drug Resistance Enzyme Induction - drug effects Humans Intracellular Fluid - drug effects Intracellular Fluid - enzymology Methotrexate - pharmacology RNA, Messenger - metabolism Tetrahydrofolate Dehydrogenase - biosynthesis Tetrahydrofolate Dehydrogenase - genetics Time Factors |
| title | The intracellular content of dihydrofolate reductase: possibilities for control and implications for chemotherapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T18%3A34%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20intracellular%20content%20of%20dihydrofolate%20reductase:%20possibilities%20for%20control%20and%20implications%20for%20chemotherapy&rft.jtitle=Advances%20in%20enzyme%20regulation&rft.au=Bastow,%20K.F.&rft.date=1984&rft.volume=22&rft.spage=15&rft.epage=26&rft.pages=15-26&rft.issn=0065-2571&rft.eissn=1873-2437&rft_id=info:doi/10.1016/0065-2571(84)90006-2&rft_dat=%3Cproquest_cross%3E81225035%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=81225035&rft_id=info:pmid/6475640&rft_els_id=0065257184900062&rfr_iscdi=true |