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Impact of p210^Bcr-Abl on Ultraviolet C Wavelength-induced DNA Damage and Repair

Departments of Bioimmunotherapy [E. L., Z. E., M. T., R. K.], Biomathematics [S. L. T.], and Leukemia [R. K.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center-Science Park/Research Division, Smithville, Texas 78957 [D. L. M., M. L.]

Recently, it was shown that both Bcr and Bcr-Abl can interact with xeroderma pigmentosum group B (XPB/ERCC3), a protein implicated in DNA repair after UV-induced damage. To further analyze the effect of Bcr-Abl on the DNA damage response, we used cell lines stably transfected with the BCR-ABL gene and their parental counterparts (MBA-1 versus MO7E and Bcr-AblT1 versus 4A2⁺-pZAP) and several assays reflecting DNA repair: the comet assay, a radioimmunoassay for cyclobutane pyrimidine dimers, and clonogenic assays. After exposure to UVC (0.5–5.0 joules m^-2), the Comet assay demonstrated greater efficiency of DNA repair in the BCR-ABL-positive cells (both MBA-1 and Bcr-AblT1) when compared with their parental counterparts. Furthermore, there was less production of the UV-induced DNA adduct—cyclobutane pyrimidine dimers—as well as a more rapid rate of disappearance of these adducts and greater UV survival (clonogenic assays) in MBA-1 cells as compared with MO7E cells. Apoptosis (annexin V-FITC/propidium iodide staining) was markedly reduced in the BCR-ABL-positive cells. These results indicate that BCR-ABL confers enhanced resistance to UV radiation-induced damage and increased efficiency of DNA repair and that these changes are associated with a protective antiapoptotic effect.

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