Identifying a Diagnostic Window for the Use of Gene Expression Profiling to Predict Acute Radiation Syndrome
| Autor: | Klaus-Rüdiger Trott, Stephanie E. Combs, Cornelius Hermann, Simone Schüle, Michael J. Atkinson, Michael Abend, Patrick Ostheim, Matthias Port, Omoleye Coker |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Biophysics Radiation Dosage 030218 nuclear medicine & medical imaging Andrology 03 medical and health sciences 0302 clinical medicine biology.animal Gene expression HARS Medicine Animals Humans Radiology Nuclear Medicine and imaging RNA Messenger Whole blood Radiation biology business.industry Gene Expression Profiling Acute Radiation Syndrome Dose-Response Relationship Radiation Fold change In vitro Gene expression profiling Gene Expression Regulation 030220 oncology & carcinogenesis Female business Whole-Body Irradiation Baboon Papio |
| Zdroj: | Radiation research. 195(1) |
| ISSN: | 1938-5404 |
| Popis: | In the event of a mass casualty radiological or nuclear scenario, it is important to distinguish between the unexposed (worried well), low-dose exposed individuals and those developing the hematological acute radiation syndrome (HARS) within the first three days postirradiation. In previous baboon studies, we identified altered gene expression changes after irradiation, which were predictive for the later developing HARS severity. Similar changes in the expression of four of these genes were observed using an in vitro human whole blood model. However, these studies have provided only limited information on the time frame of the changes after exposure in relationship to the development of HARS. In this study we analyzed the time-dependent changes in mRNA expression after in vitro irradiation of whole blood. Changes in the expression of informative mRNAs (FDXR, DBB2, POU2AF1 and WNT3) were determined in the blood of eight healthy donors (6 males, 2 females) after irradiation at 0 (control), 0.5, 2 and 4 Gy using qRT-PCR. FDXR expression was significantly upregulated (P < 0.001) 4 h after ≥0.5 Gy irradiation, with an 18-40-fold peak attained 4-12 h postirradiation which remained elevated (4-9-fold) at 72 h. DDB2 expression was upregulated after 4 h (fold change, 5-8, P < 0.001 at ≥ 0.5 Gy) and remained upregulated (3-4-fold) until 72 h (P < 0.001). The earliest time points showing a significant downregulation of POU2AF1 and WNT3 were 4 h (fold change = 0.4, P = 0.001, at 4 Gy) and 8 h (fold change = 0.3-0.5, P < 0.001, 2-4 Gy), respectively. These results indicate that the diagnostic window for detecting HARS-predictive changes in gene expression may be opened as early as 2 h for most (75%) and at 4 h postirradiation for all individuals examined. Depending on the RNA species studied this may continue for at least three days postirradiation. |
| Databáze: | OpenAIRE |
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