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    Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase.

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    Authors
    Jelínek, Jaroslav
    Fairbairn, Leslie J
    Dexter, T Michael
    Rafferty, Joseph A
    Stocking, C
    Ostertag, W
    Margison, Geoffrey P
    Affiliation
    CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
    Issue Date
    1996-03-01
    
    Metadata
    Show full item record
    Abstract
    A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony-forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.
    Citation
    Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase. 1996, 87 (5):1957-61 Blood
    Journal
    Blood
    URI
    http://hdl.handle.net/10541/95845
    PubMed ID
    8634444
    Type
    Article
    Language
    en
    ISSN
    0006-4971
    Collections
    All Paterson Institute for Cancer Research

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