ADENOVIRAL-MEDIATED WILD-TYPE P53 GENE-EXPRESSION SENSITIZES COLORECTAL-CANCER CELLS TO IONIZING-RADIATION

Wild-type p53 gene transfer into the SW620 colorectal carcinoma cell l ine was performed using the replication-defective adenovirus Ad5/CMV/p 53 to evaluate the effect of wild-type p53 expression on radiation sen sitivity, The results indicated that infection with Ad5/CMV/p53 sensit ized the cells, The survival at 2 Gy was reduced from 55 to 23%, Flow cytometric analysis of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-labeled cells and in situ TUNEL staining of xenograft tumors demonstrated an increase in labeled cells with combination treatment, indicating increased apoptosis in c ells treated with Ad5/CMV/p53 before irradiation, A significant enhanc ement of tumor growth suppression by this combination strategy was obs erved in a s.c. tumor animal model compared to p53 gene therapy alone, The delay in regrowth to control tumor size of 1000 mm(3) was 2 days for 5 Gy, 15 days for Ad5/CMV/p53, and 37 days for Ad5/CMV/p53 + 5 Gy, indicating synergistic interactions, These data indicate that the del ivery of wild-type p53 to cells with p53 mutations increases their rad iation sensitivity, and this may be accomplished by adenoviral-mediate d gene therapy.