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| Status |
Public on May 23, 2018 |
| Title |
Global gene expression in response to X rays in mice deficient in Parp1 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
There is a current interest in the development of biodosimetric methods for rapidly assessing radiation exposure in the wake of a large-scale radiological event. The initial focus of this work has largely centered on determining the exposure dose to an individual using biological indicators. Gene expression signatures are showing promise for biodosimetric application, but little is known about how these signatures might translate for the assessment of radiological injury in radiosensitive individuals, who comprise a significant fraction of the general population, and who would likely require treatment following lower doses. Using Parp1-/- mice as a model radiation sensitive genotype, we have investigated the effect of this DNA repair deficiency on the gene expression response to radiation. Although Parp1 is known to play general roles in regulating transcription, the pattern of gene expression changes observed 24 h after exposure to a potentially lethal LD50 dose of radiation was remarkably similar in the two genotypes, and indicated similar levels of activation of both the p53 and NFκB radiation response pathways. In contrast, exposure of wild-type mice to a sub-lethal dose that was equal to the LD50 dose given to the Parp1-/- mice, resulted in a reduced gene expression response. Gene expression classifiers trained on the wild-type data correctly identified all wild-type samples as unexposed, exposed to a sub-lethal dose, or exposed to a potentially lethal dose. All unexposed samples from the Parp1-/- mice were also correctly classified, and 80% of the irradiated samples were identified as exposed to a potentially lethal dose. The results of this study suggest that, at least for some genotypes, gene expression has the potential to accurately detect the extent of radiological injury, rather than being useful only as a surrogate of physical radiation dose.
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| Overall design |
Parp1-/- or wild-type mice were either exposed to a LD50/30 dose of x rays, or were sham-irradiated as controls, and then sacrificed 24h later. Wild-type mice were also exposed to the dose corresponding to LD50/30 in Parp1-/-. 5 replicates, representing individual mice, were used for each condition, with the exception of wild types exposed to the LD50/30 (8.8 Gy), for which four replicates were used.
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| Contributor(s) |
Amundson SA, Kumar S, Laiakis EC, Fornace AJ Jr |
| Citation(s) |
29746213 |
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| Submission date |
Jul 13, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Sally Amundson |
| E-mail(s) |
[email protected]
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| Organization name |
Columbia University
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| Department |
Center for Radiological Research
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| Street address |
630 W. 168th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA394112 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE101402_RAW.tar |
214.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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