Dose Response of γ Rays and Iron Nuclei for Induction of Chromosomal Aberrations in Normal and Repair-Deficient Cell Lines

• Published in: Radiation research Vol. 171; no. 6; pp. 752 - 763
• Main Authors: George, Kerry A., Hada, Megumi, Jackson, Lori J., Elliott, Todd, Kawata, Tetsuya, Pluth, Janice M., Cucinotta, Francis A.
• Format: Journal Article
• Language: English
• Published: United States Radiation Research Society 01-06-2009
• Subjects: Ataxia Telangiectasia - genetics; Cell cycle; Cell Line; Cell Line, Tumor; Cell lines; Cell nucleus; Chromosome aberrations; Chromosome Aberrations - radiation effects; Chromosomes; DNA Breaks, Double-Stranded; DNA damage; DNA Repair-Deficiency Disorders - genetics; DNA-Activated Protein Kinase - deficiency; Dose response relationship; Dose-Response Relationship, Radiation; Female; Gamma Rays - adverse effects; Humans; Iron; Linear Energy Transfer; Linear Models; Nijmegen Breakage Syndrome - genetics; Radiation damage; Radiation Dosage; Radiation dose response relationship; Regression Analysis; REGULAR ARTICLES
• ISSN: 0033-7587; 1938-5404
• DOI: 10.1667/RR1680.1

George, K. A., Hada, M., Jackson, L. J., Elliott, T., Kawata, T., Pluth, J. M. and Cucinotta, F. A. Dose Response for c Rays and Iron Nuclei for Induction of Chromosomal Aberrations in Normal and Repair-Deficient Cell Lines. Radiat. Res. 171, 752–763 (2009). We studied the effects of DNA double-strand break (DSB) repair deficiencies on chromosomal aberration frequency using low doses (<1 Gy) of γ rays and high-energy iron ions (LET  =  151 keV/µm). Chromosomal aberrations were measured using the fluorescence whole-chromosome painting technique. The cell lines included fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) and gliomablastoma cells proficient in or lacking DNA-dependent protein kinase (DNA-PK) activity. The yields of both simple and complex chromosomal aberrations were increased in DSB repair-defective cells compared to normal cells; the increase was more than twofold higher for γ rays compared to iron nuclei. For γ-ray-induced aberrations, the ATM- and NBS-defective lines were found to have significantly larger quadratic components compared to normal fibroblasts for both simple and complex aberrations, while the linear dose–response term was significantly higher only for the NBS cells. For simple and complex aberrations induced by iron nuclei, regression models preferred purely linear and quadratic dose responses, respectively, for each cell line studied. RBEs were reduced relative to normal cells for all of the DSB repair-defective lines, with the DNA-PK-deficient cells found to have RBEs near unity. The large increase in the quadratic dose–response terms in the DSB repair-deficient cell lines points to the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and to minimize aberration formation. The differences found between AT and NBS cells at lower doses suggest important questions about the applicability of observations of radiation sensitivity at high doses to low-dose exposures.