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

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    Authors
    Kinsella, Anne R
    Haran, M Sally
    Affiliation
    Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom.
    Issue Date
    1991-04-01
    
    Metadata
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    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.
    Citation
    Decreasing sensitivity to cytotoxic agents parallels increasing tumorigenicity in human fibroblasts. 1991, 51 (7):1855-9 Cancer Res.
    Journal
    Cancer Research
    URI
    http://hdl.handle.net/10541/104675
    PubMed ID
    2004369
    Type
    Article
    Language
    en
    ISSN
    0008-5472
    Collections
    All Paterson Institute for Cancer Research

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