Misrepair of DNA double-strand breaks in patient with unidentified chromosomal fragility syndrome and family history of radiosensitivity. (January 2014)

• Record Type: Journal Article
• Authors: Alsbeih, Ghazi; Brock, Williams; Story, Michael
• Is Part Of: International journal of radiation biology. Volume 90:Number 1(2014:Jan.)
• Page Start: 53
• Page End: 59
• Publication Date: 2014-01
• Subjects: Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.3109/09553002.2014.859764
• Languages: English
• ISSNs: 0955-3002

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: To test the hypothesis that differences in DNA double-strand breaks (DSB) repair fidelity underlies differences in radiosensitivity.</p> <p> <italic>Materials and methods:</italic> A primary fibroblast culture (C42) derived from a pediatric cancer patient treated with reduced radiation doses consequent to a family history of radiosensitivity reminiscent of chromosomal fragility syndrome, was compared to a normal control (C29). DNA DSB rejoining and repair fidelity were studied by Southern blotting and hybridization to specific fragments: <italic>Alu</italic> repetitive sequence representing the overall DSB rejoining capacity in the genome and a 3.2 Mbp <italic>Not</italic>I restriction fragment on chromosome 21 for DSB repair fidelity.</p> <p> <italic>Results</italic>: Although both assays showed statistically significant difference (<italic>p</italic> ≤ 0.05) between the two cell strains in residual misrepaired (un-or mis-rejoined) DSB (24 h after 30 or 80 Gy), the residual damage was lower in the <italic>Alu</italic> enriched genome assay compared to <italic>Not</italic>I assay (0.01–0.07 and 0.10–0.37, respectively).</p> <p> <italic>Conclusions</italic>: These results suggest that, in comparison to classic DSB repair experiment, an assay of measuring DNA DSB repair fidelity can provide better resolution and a more accurate estimate of misrepair of radiation-induced DNA damage, which underlies genomic instability and increased radiosensitivity.</p> </abstract>