In a nuclear or radiological event, an early diagnostic or prognostic tool is needed to distinguish unexposed from low-and highly-exposed individuals with the latter requiring early and intensive medical care. Radiation-induced gene expression (GE) changes observed within hours and days after irradiation have shown potential to serve as biomarkers for either dose reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of GE markers lies in their capability for early (1-3 day after irradiation), high-throughput, and point-of-care diagnosis required for the prediction of the acute radiation syndrome (ARS).
ConclusionsAs a key session of the ConRad conference in 2021, experts from different institutions were invited to provide state-of-the-art information on a range of topics including: (1) Biodosimetry: What are the current efforts to enhance the applicability of this method to perform retrospective biodosimetry? (2) Effect Prediction: Can we apply radiation-induced GE changes for prediction of acute health effects as an approach, complementary to and integrating retrospective dose estimation? (3) High-throughput and Point-of-Care Diagnostics: What are the current developments to make the GE approach applicable as a high-throughput as well as a point-of-care diagnostic platform? (4) Low Level Radiation: What is the lowest dose range where GE can be used for biodosimetry purposes? (5) Methodological Considerations: Different aspects of radiation-induced GE related to more detailed analysis of exons, transcripts and next-generation sequencing (NGS) were reported.
Computed tomography (CT) is a crucial element of medical imaging diagnostics. The widespread application of this technology has made CT one of the major contributors to medical radiation burden, despite the fact that doses per individual CT scan steadily decrease due to the advancement of technology. Epidemiological risk assessment of CT exposure is hampered by the fact that moderate adverse effects triggered by low doses of CT exposure are likely masked by statistical fluctuations. In light of these limitations, there is need of further insights into the biological processes induced by CT scans to complement the existing knowledge base of risk assessment. This prompted us to investigate the early transcriptomic response of ex vivo irradiated peripheral blood of three healthy individuals. Samples were irradiated employing a modern dual-source-CT-scanner with a tube voltage of 150 kV, resulting in an estimated effective dose of 9.6 mSv. RNA was isolated 1 h and 6 h after exposure, respectively, and subsequently analyzed by RNA deep sequencing. Differential gene expression analysis revealed shared upregulation of AEN, FDXR, and DDB2 6 h after exposure in all three probands. All three genes have previously been discussed as radiation responsive genes and have already been implicated in DNA damage response and cell cycle control after DNA damage. In summary, we substantiated the usefulness of AEN, FDXR, and DDB2 as RNA markers of low dose irradiation. Moreover, the upregulation of genes associated with DNA damage reminds one of the genotoxic nature of CT diagnostics even with the low doses currently applied.
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