Decreasing sensitivity to cytotoxic agents parallels increasing tumorigenicity in human fibroblasts.

2.50
Hdl Handle:
http://hdl.handle.net/10541/104675
Title:
Decreasing sensitivity to cytotoxic agents parallels increasing tumorigenicity in human fibroblasts.
Authors:
Kinsella, Anne R; Haran, M Sally
Abstract:
Human 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.
Affiliation:
Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom.
Citation:
Decreasing sensitivity to cytotoxic agents parallels increasing tumorigenicity in human fibroblasts. 1991, 51 (7):1855-9 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Apr-1991
URI:
http://hdl.handle.net/10541/104675
PubMed ID:
2004369
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKinsella, Anne Ren
dc.contributor.authorHaran, M Sallyen
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.en
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

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