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.

Comparative analysis of physical doses and biomarker changes in subjects underwent Computed Tomography, Positron Emission Tomography-Computed Tomography, and interventional procedures.

Even though the medical uses of ionizing radiation are well-acknowledged globally as vital tools for the improvement of human health, they also symbolize the major man-made sources of radiation exposure to the population. Estimation of absorbed dose and biological changes after radiation-based imaging might help to better understand the effects of low dose radiation. Because of this, we measured the Entrance Surface Dose (ESD) at different anatomical locations using Lithium tetraborate doped with manganese (Li2B4O7: Mn), recorded Dose Length Product (DLP) and Dose Area Product (DAP), analyzed Chromosomal Aberration (CA), Micronucleus (MN), gamma-H2AX (γ-H2AX), and p53ser15 proteins in the blood lymphocytes of patients (n = 267) underwent Computed Tomography (CT), Positron Emission Tomography-CT (PET/CT), and interventional procedures and healthy volunteers (n = 19). The DLP and effective doses obtained from PET/CT procedures were significantly higher (p < 0.05) when compared to CT. Fluoroscopic time and DAP were significantly higher (p < 0.05) in therapeutic compared to diagnostic interventional procedures. All the anatomical locations registered a significant amount of ESD, the ESD obtained from CT and interventional procedures were significantly (p < 0.05) higher when compared to PET/CT. Fluoroscopic time did not correlate with the ESD (eye, head, thyroid, and shoulder; R2 = 0.03). CA frequency after PET/CT was significantly higher (p < 0.001) when compared to CT and interventional procedures. MN frequency was significantly higher in 24-hs (p < 0.001) post-interventional procedure compared to 2-hs. The mean ± SD of mean fluorescence intensity of γ-H2AX and p53ser15 obtained from all subjects underwent PET/CT and interventional procedures did not show a significant difference (p > 0.05) between pre- and post-procedure. However, the relative fluorescence intensity of γ-H2AX and p53ser15 was >1 in 58.5 % and 65.8 % of subjects respectively. Large inter-individual variation and lack of correlation between physical dose and biomarkers suggest the need for robust dosimetry with a large sample size to understand the health effects of low dose radiation.

Exposure of patients to low doses of X-radiation during neuro-interventional imaging and procedures: Dose estimation and analysis of γ-H2AX foci and gene expression in blood lymphocytes.

Radiation has widespread applications in medicine. However, despite the benefits of medical radiation exposures, adverse long-term health effects are cause for concern. Protein and gene biomarkers are early indicators of cellular response after low-dose exposure. We examined DNA damage by quantifying γ-H2AX foci and expression of twelve candidate genes in the blood lymphocytes of patients exposed to low doses of X-radiation during neuro-interventional procedures. Entrance surface dose (ESD; 10.92-1062.55 mGy) was measured by thermoluminescence dosimetry (TLD). Absorbed dose was estimated using γ-H2AX focus frequency and gene expression, with in vitro dose-response curves generated for the same biomarkers. γ-H2AX foci in post-exposure samples were significantly higher than in pre-exposure samples. Among the genes analysed, FDXR, ATM, BCL2, MDM2, TNFSF9, and PCNA showed increased expression; CDKN1A, DDB2, SESN1, BAX, and TNFRSF10B showed unchanged or decreased expression. Absorbed dose, estimated based on γ-H2AX focus frequency and gene expression changes, did not show any correlation with measured ESD. Patients undergoing interventional procedures receive considerable radiation doses, resulting in DNA damage and altered gene expression. Medical procedures should be carried out using the lowest radiation doses possible without compromising treatment.

DNA damage and gene expression changes in patients exposed to low-dose X-radiation during neuro-interventional radiology procedures.

Interventional radiology-based imaging is the preferred choice for diagnosis and therapy of many complex diseases, despite possible adverse effects of the radiation exposures. We have measured induced DNA damage and changes in gene expression in relation to entrance surface dose (ESD) in peripheral blood samples of patients (n = 51) who underwent neuro-interventional radiological procedures. The ESD values, measured by thermoluminescence dosimetry, were 4.9-273 mGy (forehead), 14-398 mGy (eyes), 8-433.3 mGy (shoulders), and 4.7-242.5 mGy (thyroid). The in-built recorded Dose Area Product (DAP) values were 74.61-558.55 and 13.17-2825.12 Gy*cm2 for diagnostic and therapeutic procedures, respectively. The mean fluorescence intensity (MFI) on the phosphorylation of γ-H2AX and p53ser-15 was higher in samples obtained post-exposure vs. pre-exposure. However, the increase was statistically significant only for p53ser-15 (P < 0.01). Consistent with γ-H2AX, CDKN1A, FDXR, BAX, DDB2, SESN1, BCL2, MDM2, TNFSF10B, and PCNA showed (non-significant) decreased expression while GADD45A, ATM, and TNFSF9 showed (non-significant) increased expression. Our results suggest that most of the patients had increased DNA damage and altered gene expression after receiving relatively low doses of ionising radiation. This implies that these procedures should be carried out at the lowest possible doses of radiation that do not compromise image quality.

18F-FDG PET/CT scanning: Biological effects on patients: Entrance surface dose, DNA damage, and chromosome aberrations in lymphocytes.

Positron Emission Tomography/Computed Tomography (PET/CT), a combination of PET and CT, is used in tumor staging, therapy planning, and treatment response monitoring. During PET imaging, patients receive low doses of radiation, which can induce an adaptive response and necessitate higher doses for therapeutic efficacy. Higher doses may augment toxicity to normal cells. We are examining the effects of short-term, low-dose exposures to ionizing radiation. Entrance Surface Dose (ESD) to head, shoulders, and pelvis regions were measured using Li2B4O7: Mn thermoluminescent dosimeters. Induced DNA damage in lymphocytes was measured using γ-H2AX, p53Ser-15, chromosome aberrations, and micronucleus formation in subjects (n = 25) who underwent 18F-FDG PET/CT. The mean ESD ± SD value obtained were 32.40 ± 16.86, 32.58 ± 14.22, 32.02 ± 15.42, 43.55 ± 18.25 and 42.80 ± 24.67 mGy for the head, right shoulder, left shoulder, right pelvic, and left pelvic regions, respectively. The effective doses of PET and CT ranged from 4.01 to 6.61 and 16.40-72.18 mSv, respectively, and the obtained Dose Length Product (DLP) varied from 1093 to 4812 mGy*cm. There was no correlation between DLP and ESD (r2 = 0.1). The chromosome aberration assay showed a significant increase (p < 0.05), post-scanning vs. pre-scanning; the γ-H2AX, p53Ser-15, and micronucleus assays did not show significant increases. Induced DNA damage showed inter-individual variation among the study subjects. Our results imply that the patients received a biologically significant dose during 18F-PET/CT scanning and precautions may be needed to reduce any long-term risk of exposure.