Molecular Determinants of Radioresponse in Prostate Cancer
Annual rept. 1 Aug 2001-31 Jul 2002
UNIVERSITY HEALTH NETWORK TORONTO (ONTARIO) GRANT AND CONTRACT SERVICES
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The overall hypothesis of this project is that the radiation response of normal and cancerous prostate tissues can be correlated to the appropriate sensing and repair of DNA breaks by repair complexes following exposure to ionizing radiation. Specific aims relate to determining the interaction of DNA repair proteins in vitro using immunofluorescence confocal microscopy and biochemical DNA rejoining assays under both hypoxic and oxic conditions given in vivo tumor cell populations. An in vivo program of prostate xenograft radioresponse is also being initiated to determine the level of DNA repair in situ using immunohistochemistry and immunofluorescence markers. Our studies show that terminal growth arrest rather than apoptosis is the major death pathway for irradiated prostate cancer cells and that prostate cancer cells have a DNA repair defect when compared to normal prostate epithelial cells. This appears to be related to the expression and intracellular function of the rad51 protein.
- Medicine and Medical Research