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

Visweswaran, Shangamithra; Joseph, Santhosh; Dhanasekaran, Jagadeesan; Paneerselvam, S.; Annalakshmi, O.; Jose, M.T.; Prakash, Venkatachalam

doi:10.1016/j.mrgentox.2020.503237

Cited by 11 publications

(10 citation statements)

References 40 publications

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“…Participants who underwent radiation-based imaging/therapy were used as a model to test the suitability of the biomarkers for reliable biodosimetry [Bhavani et al, 2014;Raavi et al, 2019;Thierens et al, 1995]. In line with the literature, our lab also reported that the participants received a considerable dose during medical imaging [Kanagaraj et al, 2015;Prasad et al, 2019;Visweswaran et al, 2020]. We have adopted a similar approach to examine the suitability of CDKN1A, DDB2, FDXR, and PCNA genes expression for radiation triage; analysis of those genes in the blood samples shows that the expression level of those genes in pre-imaging did not differ significantly when compared to healthy participants as well as participants with inflammatory condition (shown in Fig.…”

Section: Discussionmentioning

confidence: 55%

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

Kannan¹,

Koshy²,

Raavi³

et al. 2023

Cytogenet Genome Res

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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.

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Section: Discussionmentioning

confidence: 55%

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

Kannan¹,

Koshy²,

Raavi³

et al. 2023

Cytogenet Genome Res

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“…Previous studies have shown that DDB2 was a radiative biomarker. However, most of them were focused on sequencing and screening and lack of detailed studies on time-dose effect (29). Therefore, our study steps to the other four differentially expressed genes, DDB2, AEN, TRIAP1 and TRAF4 and explore their feasibility as biomarkers for early response to ionizing radiation damage.…”

Section: Resultsmentioning

confidence: 99%

Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Zhou²,

Meng³

et al. 2022

Life

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Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2–24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

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“…(continued.) methodology), teams used only 1-4 genes [54,[64][65][66][67][68][69][70][71][72][73]. Large scale inter-laboratory comparison exercises initiated from NATO research task groups or the European biodosimetry network (RENEB) confirmed the applicability of this approach [74][75][76][77].…”

Section: Ge Biomarkers For Retrospective Biodosimetrymentioning

confidence: 91%

“…Many laboratories worldwide established their own gene set comprising 1-4 genes for dose estimation using qRT-PCR [54,[64][65][66][67][68][69][70][71][72][73]. Dose estimation requires a calibration curve comprising irradiated samples examined at the same time after irradiation as the potentially irradiated samples of some radiation victims.…”

Section: Current Strategies On Dealing With Biomarkers Associated Cha...mentioning

confidence: 99%

Early molecular markers for retrospective biodosimetry and prediction of acute health effects

et al. 2022

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Radiation-induced biological changes occurring within hours and days after irradiation can be potentially used for either exposure reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of molecular protein or gene expression (GE) (mRNA) marker lies in their capability for early (1–3 days after irradiation), high-throughput and point-of-care diagnosis, required for the prediction of the acute radiation syndrome (ARS) in radiological or nuclear scenarios. These molecular marker in most cases respond differently regarding exposure characteristics such as e.g. radiation quality, dose, dose rate and most importantly over time. Changes over time are in particular challenging and demand certain strategies to deal with. With this review, we provide an overview and will focus on already identified and used mRNA GE and protein markers of the peripheral blood related to the ARS. These molecules are examined in light of ‘ideal’ characteristics of a biomarkers (e.g. easy accessible, early response, signal persistency) and the validation degree. Finally, we present strategies on the use of these markers considering challenges as their variation over time and future developments regarding e.g. origin of samples, point of care and high-throughput diagnosis.

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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

Cited by 11 publications

References 40 publications

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

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

Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Early molecular markers for retrospective biodosimetry and prediction of acute health effects

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