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    Effects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation.

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    Authors
    Hendry, Jolyon H
    Broadbent, D A
    Roberts, Stephen A
    Potten, Christopher S
    Affiliation
    Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK. JHendry@PICR.MAN.AC.UK
    Issue Date
    2000-04
    
    Metadata
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    Abstract
    PURPOSE: To study the role of p53 and bcl-2 in the response of the small intestine to irradiation delivered at low dose-rate. MATERIALS AND METHODS: Mice homozygous for p53 or bcl-2 deletion (-/-), their respective heterozygotes (+/-), and their wild-type littermates (+/+) including a previously used hybrid strain (B6D2F1), were irradiated to the whole-body using 60Co gamma-rays at 1 Gy h(-1). Crypt survival levels in the small intestine were measured at day 3 after the end of irradiation. RESULTS: Crypt survival levels were higher in p53 -/- mice than in the other p53 genotypes after 25-30 Gy, but not after lower or higher doses. Similar experiments with the three genotypes for bcl-2 status showed lower crypt survival after all doses used in the -/- mice, compared with the +/- and +/+ mice, which were similar in response. The marked degree of curvature in the survival curve observed for the p53 genotypes was also observed in B6D2F1 hybrid mice, was particularly striking in the p53 -/- mice, but was not seen to the same extent in the bcl-2 genotypes. The heterozygotes for p53 or for bcl-2 were nearer in response to their respective +/+ genotypes rather than the -/- genotypes. CONCLUSION: The increased crypt survival levels at some radiation dose levels in the p53 nulls contrasts with the lack of change reported previously using irradiation at high dose-rate. The decreased survival in the bcl-2 nulls is consistent with the known 'survival' function of bcl-2, although bcl-2 expression has not been detected immunohistochemically in this intestinal site. The marked degree of curvature in the dose-response curve at high dose levels for some genotypes was unexpected at this low dose-rate.
    Citation
    Effects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation. 2000, 76 (4):559-65 Int. J. Radiat. Biol.
    Journal
    International Journal of Radiation Biology
    URI
    http://hdl.handle.net/10541/88619
    DOI
    10.1080/095530000138574
    PubMed ID
    10815637
    Type
    Article
    Language
    en
    ISSN
    0955-3002
    ae974a485f413a2113503eed53cd6c53
    10.1080/095530000138574
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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