Show simple item record

dc.contributor.authorKinsella, Anne R
dc.contributor.authorHaran, M Sally
dc.date.accessioned2010-06-11T08:56:10Z
dc.date.available2010-06-11T08:56:10Z
dc.date.issued1991-04-01
dc.identifier.citationDecreasing sensitivity to cytotoxic agents parallels increasing tumorigenicity in human fibroblasts. 1991, 51 (7):1855-9 Cancer Res.en
dc.identifier.issn0008-5472
dc.identifier.pmid2004369
dc.identifier.urihttp://hdl.handle.net/10541/104675
dc.description.abstractHuman embryo fibroblasts of common genetic origin but exhibiting a range of phenotypes from normal to aggressively tumorigenic have been used to study resistance to the cytotoxic drugs methotrexate and N-(phosphonacetyl)-L-aspartate. Measurement of the intrinsic sensitivities of these cells to the two drugs in standard survival assays, in normal fetal bovine serum, showed increasing resistance to parallel increasing tumor-igenicity. Tumor cells were totally resistant to 10 mM N-(phosphonacetyl)-L-aspartate whereas the 50% lethal dose for methotrexate for the tumor cells was 500 nM compared with 50 nM for the normal diploid parent cell line. The difference in resistance between the immortal and tumorigenic cell lines was eliminated for both methotrexate and N-(phosphonacetyl)-L-aspartate, when the experiments were repeated in the presence of dialyzed fetal bovine serum, but could be restored by the addition of either hypoxanthine (100 microM) or uridine (10 microM). This suggested an important role for the salvage pathways of purine and pyrimidine biosynthesis in the increased resistance of the more tumorigenic cell lines. The implications of these data in relation to cancer chemotherapy will be discussed.
dc.language.isoenen
dc.subjectCancerous Cell Transformationen
dc.subject.meshAspartic Acid
dc.subject.meshCell Line
dc.subject.meshCell Line, Transformed
dc.subject.meshCell Transformation, Neoplastic
dc.subject.meshDrug Resistance
dc.subject.meshFibroblasts
dc.subject.meshGene Amplification
dc.subject.meshHumans
dc.subject.meshMethotrexate
dc.subject.meshPhenotype
dc.subject.meshPhosphonoacetic Acid
dc.titleDecreasing sensitivity to cytotoxic agents parallels increasing tumorigenicity in human fibroblasts.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom.en
dc.identifier.journalCancer Researchen
html.description.abstractHuman embryo fibroblasts of common genetic origin but exhibiting a range of phenotypes from normal to aggressively tumorigenic have been used to study resistance to the cytotoxic drugs methotrexate and N-(phosphonacetyl)-L-aspartate. Measurement of the intrinsic sensitivities of these cells to the two drugs in standard survival assays, in normal fetal bovine serum, showed increasing resistance to parallel increasing tumor-igenicity. Tumor cells were totally resistant to 10 mM N-(phosphonacetyl)-L-aspartate whereas the 50% lethal dose for methotrexate for the tumor cells was 500 nM compared with 50 nM for the normal diploid parent cell line. The difference in resistance between the immortal and tumorigenic cell lines was eliminated for both methotrexate and N-(phosphonacetyl)-L-aspartate, when the experiments were repeated in the presence of dialyzed fetal bovine serum, but could be restored by the addition of either hypoxanthine (100 microM) or uridine (10 microM). This suggested an important role for the salvage pathways of purine and pyrimidine biosynthesis in the increased resistance of the more tumorigenic cell lines. The implications of these data in relation to cancer chemotherapy will be discussed.


This item appears in the following Collection(s)

Show simple item record