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    Engineering drug resistance in human cells.

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    Authors
    Fairbairn, Leslie J
    Rafferty, Joseph A
    Lashford, Linda S
    Affiliation
    Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.
    Issue Date
    2000-05
    
    Metadata
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    Abstract
    Many of the problems with current anti-tumour therapies stem from a lack of specificity for tumour as opposed to normal tissues. To address the problem of collateral toxicity during anti-tumour chemotherapy we have been developing a gene therapy approach to protect normal tissues from the toxic and potentially mutagenic effects of chemotherapeutic agents. As a paradigm for this we have been examining the potential of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) to confer genetic chemoprotection to the bone marrow. By transfer and expression of a mutant form of this protein, which is resistant to inactivation by the tumour sensitising agent O6-benzylguanine (O6-beG), we have been able to demonstrate protection of murine bone marrow in vitro from the cytotoxic and clastogenic effects of O6-beG in combination with the anti-tumour agent temozolomide. This protection is seen in multiple lineages, including erythroid and granulocyte/macrophage progenitors, as well as more primitive cells. Importantly, significant protection of the platelet lineage is also seen, with faster recovery of platelets. The multi-lineage protection seen has encouraged us to take this approach forward to clinical trial in the near future.
    Citation
    Engineering drug resistance in human cells. 2000, 25 Suppl 2:S110-3 Bone Marrow Transplant.
    Journal
    Bone Marrow Transplantation
    URI
    http://hdl.handle.net/10541/86686
    PubMed ID
    10933202
    Type
    Article
    Language
    en
    ISSN
    0268-3369
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

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