Candidate Gene Expression in Regional Population and Its Relevance for Radiation Triage.

Quantification of gene expression signatures has been substantiated as a potential and rapid marker for radiation triage and biodosimetry during nuclear emergencies. Similar to the established biodosimetry assays, the gene expression assay has drawbacks such as being highly dynamic and transient, not specific to ionizing radiation, and also influenced by confounding factors such as gender, health status, lifestyle, and inflammation. In view of that, prior knowledge of baseline expression of certain candidate genes in a population could complement the discrimination of the unexposed from the exposed individuals without the need for individual pre-exposure controls. We intended to establish a baseline expression of reported radiation-responsive genes such as CDKN1A, DDB2, FDXR, and PCNA in the blood samples of healthy human participants and then compare it with diabetic/hypertension participants (as a chronic inflammatory condition) drawn from south Indian population. Further, we have examined the appropriateness of the assay for radiation triage-like situations; i.e., the expression profiles of those genes were examined in the participants who underwent X-ray-based medical imaging. Acute inflammation induced by lipopolysaccharide exposure in the blood significantly increased the fold expression of those genes (p < 0.0001) compared to the control. Whereas the basal expression level of those genes among the participants with the inflammatory condition is marginally higher than those observed in the healthy participants; despite the excess, the fold increase in those genes between the groups did not differ significantly. Consistent with the inflammatory participants, the basal expression level of those genes in the blood sample of participants who received X-radiation during neuro-interventional and computed tomography imaging is marginally higher than those observed in the pre-exposure of respective groups. Nevertheless, the fold increase in those genes did not differ significantly as the fold change fell within the two folds. Thus, overall results suggest that the utility of CDKN1A, DDB2, FDXR, and PCNA gene expression for radiation triage specific after very low-dose radiation exposure needs to be interpreted with caution for a much more reliable triage.

Enhanced γ-H2AX Foci Frequency and Altered Gene Expression in Participants Exposed to Ionizing Radiation During I-131 Nuclear Medicine Procedures.

Purpose: Ionizing radiation-based technologies are extensively used in the diagnosis and treatment of diseases. While utilizing the technologies, exposure to a certain amount of radiation is unavoidable. Data can be obtained from participants who received radiation during medical imaging and therapeutic purposes to predict the effects of low-dose radiation. Methods: To understand the effects of low-dose radiation, participants (n = 22) who received radioactive I-131 for scan/therapy were used as a model in this study. Blood samples were drawn pre- and post-administration of I-131. Biological effects were measured using markers of DNA damage (γ-H2AX, micronucleus (MN), and chromosomal aberrations (CA)) and response to damage through gene expression changes (ATM, CDKN1A, DDB2, FDXR, and PCNA) in blood samples. Results: Mean frequency of γ-H2AX foci in pre-samples was 0.28 ± 0.16, and post-samples were 1.03 ± 0.60. γ-H2AX foci frequency obtained from post-samples showed significant (p < 0.0001) and a heterogeneous increase in all the participants (received I-131 for scan/therapy) when compared to pre-samples. A significant increase (p < 0.0001) in MN and CA frequency was also observed in participants who received the I-131 therapy. Gene expression analysis indicates that all genes (ATM, CDKN1A, DDB2, FDXR, and PCNA) were altered in post-samples, although with varying degrees, suggesting that the cellular responses to DNA damage, such as damage repair, cell cycle regulation to aid in repair and apoptosis are increased, which priority is given to repair, followed by apoptosis. Conclusion: The results of this study indicate that the participants who received I-131 (low doses of ß- and γ-radiation) can produce substantial biological effects.