PARENT SESSION
1:30 PM to 3:30 PM
Monday, April 22, 2002
Poster Session 12 DNA Damage and Repair I
Room: Nevada Exhibition Center
(P17-167) The role of homologous recombination in the repair of radiation-induced DNA double-strand breaks in human tumor cell lines.
Galloway, Anne*,1, Allalunis-Turner, Joan1,2, 1 Department of Experimental Oncology, Edmonton, Alberta2 Department of Oncology, Edmonton, Alberta
ABSTRACT-
Intrinsic tumor cell radioresistance can contribute to failure to achieve local tumor control following radiotherapy. Research directed at producing adjunct therapies that would create radiation-sensitivity has focused on the non-homologous end-joining pathway of double-strand break repair (DSBR), a process dependent on the DNA-PK holoenzyme. However, recent studies have indicated that homologous recombination (HR) may contribute to DSBR in human tumor cells, most significantly in those tumors in which p53 is mutated. We have previously established two human glioma cell lines that differ in their ability to repair double-strand breaks. M059J, which lacks DNA-PKcs, is radiation-sensitive and DSBR-deficient. M059K has normal DNA-PKcs and is DSBR-proficient. Both lines are p53 mutant. Using these parental lines, as well as a p53+/DNA-PK+ human glioma cell line and an inducible vector system, we have established transfected lines which, when induced, express anti-sense RNA to one of the several genes involved in the HR repair pathway. In some instances, we have been able to create "short-term knock-outs" of these often essential gene products, reducing protein levels to near undetectable. These "short-term knock-out" lines are being used to assess radiation sensitivity, total DSBR, and the types of repair products formed in these various genetic backgrounds, with the ultimate aim of enhancing our understanding of DNA repair in tumor cells and of finding new therapeutic targets in the treatment of malignant glioma. Supported by an award from the Alberta Cancer Foundation.
KEYWORDS: DNA repair, homologous recombination, anti-sense