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    Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.

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    Authors
    Potten, Christopher S
    Booth, Dawn
    Haley, J D
    Affiliation
    Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
    Issue Date
    1997
    
    Metadata
    Show full item record
    Abstract
    The gastrointestinal tract, with its rapid cell replacement, is sensitive to cytotoxic damage and can be a site of dose-limiting toxicity in cancer therapy. Here, we have investigated the use of one growth modulator to manipulate the cell cycle status of gastrointestinal stem cells before cytotoxic exposure to minimize damage to this normal tissue. Transforming growth factor beta-3 (TGF-beta3), a known inhibitor of cell cycle progression through G1, was used to alter intestinal crypt stem cell sensitivity before 12-16 Gy of gamma irradiation, which was used as a model cytotoxic agent. Using a crypt microcolony assay as a measure of functional competence of gastrointestinal stem cells, it was shown that the administration of TGF-beta3 over a 24-h period before irradiation increased the number of surviving crypts by four- to six-fold. To test whether changes in crypt survival are reflected in the well-being of the animal, survival time analyses were performed. After 14.5 Gy of radiation, only 35% of the animals survived within a period of about 12 days, while prior treatment with TGF-beta3 provided significant protection against this early gastrointestinal animal death, with 95% of the treated animals surviving for greater than 30 days.
    Citation
    Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo. 1997, 75 (10):1454-9 Br. J. Cancer
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/95178
    PubMed ID
    9166937
    Type
    Article
    Language
    en
    ISSN
    0007-0920
    Collections
    All Paterson Institute for Cancer Research

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