Abstract | PURPOSE: To test the hypothesis that differences in DNA double-strand breaks ( DSB) repair fidelity underlies differences in radiosensitivity. MATERIALS AND METHODS: 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: Alu repetitive sequence representing the overall DSB rejoining capacity in the genome and a 3.2 Mbp NotI restriction fragment on chromosome 21 for DSB repair fidelity. RESULTS: Although both assays showed statistically significant difference (p ≤ 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 Alu enriched genome assay compared to NotI assay (0.01-0.07 and 0.10-0.37, respectively). CONCLUSIONS: 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.
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Authors | Ghazi Alsbeih, Williams Brock, Michael Story |
Journal | International journal of radiation biology
(Int J Radiat Biol)
Vol. 90
Issue 1
Pg. 53-9
(Jan 2014)
ISSN: 1362-3095 [Electronic] England |
PMID | 24164476
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Topics |
- Base Pair Mismatch
(genetics, radiation effects)
- Biological Assay
(methods)
- Child, Preschool
- Chromosome Disorders
(genetics)
- Chromosome Fragility
(genetics, radiation effects)
- DNA Damage
(genetics)
- DNA Mismatch Repair
(genetics, radiation effects)
- Female
- Humans
- Radiation Tolerance
(genetics)
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