Dose response of gamma rays and iron nuclei for induction of chromosomal aberrations in normal and repair-deficient cell lines.
We studied the effects of DNA double-strand break (DSB) repair deficiencies on chromosomal aberration frequency using low doses (<1 Gy) of gamma rays and high-energy iron ions (LET = 151 keV/microm). 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 gamma rays compared to iron nuclei. For gamma-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.
George
Kerry A
KA
Wyle, Houston, Texas 77058, USA.
Hada
Megumi
M
Jackson
Lori J
LJ
Elliott
Todd
T
Kawata
Tetsuya
T
Pluth
Janice M
JM
Cucinotta
Francis A
FA
D001260:Ataxia Telangiectasia / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics; D051747:DNA-Activated Protein Kinase / Q000172:deficiency; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D007501:Iron; D018499:Linear Energy Transfer; D016014:Linear Models; D049932:Nijmegen Breakage Syndrome / Q000235:genetics; D011829:Radiation Dosage; D012044:Regression Analysis
D007501:Iron; D051747:DNA-Activated Protein Kinase