Biomarkers of Ionizing Radiation Exposure: A Multiparametric Approach

Zeegers, Dimphy; Somasundaram, Venkatesan; Koh, Shu Wen; Low, Grace Kah Mun; Srivastava, P.C.; Sundaram, Neisha; Sethu, Swaminathan; Banerjee, Birendranath; Manikandan, Jayapal; Belyakov, O.V.; Baskar, Rajamanickam; Balajee, Adayabalam S.; Hande, M. Prakash

doi:10.4103/2041-9414.198911

Cited by 39 publications

(18 citation statements)

References 27 publications

(27 reference statements)

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“…Zeegers et al compared suitability of different current biodosimetric markers. Although they performed their study on a cell line and not in vivo they conclusions strongly encouraged the idea of employing a multiparametric approach for dose/risk estimation [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood

et al. 2018

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The increasing risk of acute large-scale radiological/nuclear exposures of population underlines the necessity of developing new, rapid and high throughput biodosimetric tools for estimation of received dose and initial triage. We aimed to compare the induction and persistence of different radiation exposure biomarkers in human peripheral blood in vivo. Blood samples of patients with indicated radiotherapy (RT) undergoing partial body irradiation (PBI) were obtained soon before the first treatment and then after 24 h, 48 h, and 5 weeks; i.e. after 1, 2, and 25 fractionated RT procedures. We collected circulating peripheral blood from ten patients with tumor of endometrium (1.8 Gy per fraction) and eight patients with tumor of head and neck (2.0–2.121 Gy per fraction). Incidence of dicentrics and micronuclei was monitored as well as determination of apoptosis and the transcription level of selected radiation-responsive genes. Since mitochondrial DNA (mtDNA) has been reported to be a potential indicator of radiation damage in vitro, we also assessed mtDNA content and deletions by novel multiplex quantitative PCR. Cytogenetic data confirmed linear dose-dependent increase in dicentrics (p < 0.01) and micronuclei (p < 0.001) in peripheral blood mononuclear cells after PBI. Significant up-regulations of five previously identified transcriptional biomarkers of radiation exposure (PHPT1, CCNG1, CDKN1A, GADD45, and SESN1) were also found (p < 0.01). No statistical change in mtDNA deletion levels was detected; however, our data indicate that the total mtDNA content decreased with increasing number of RT fractions. Interestingly, the number of micronuclei appears to correlate with late radiation toxicity (r2 = 0.9025) in endometrial patients suggesting the possibility of predicting the severity of RT-related toxicity by monitoring this parameter. Overall, these data represent, to our best knowledge, the first study providing a multiparametric comparison of radiation biomarkers in human blood in vivo, which have potential for improving biological dosimetry.

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Section: Discussionmentioning

confidence: 99%

The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood

et al. 2018

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“…However, common (bio-) markers that are associated with plasma treatment are missing. Along similar lines, there is an unmet need for the identification of markers for other types of therapies including ionizing radiation [ 23 ] and photodynamic therapy (PDT) [ 24 ]. Established markers would allow not only tracking, but also for quantifying the therapeutic efficacy of a given treatment.…”

Section: Introductionmentioning

confidence: 99%

Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

et al. 2018

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Increasing numbers of cancer deaths worldwide demand for new treatment avenues. Cold physical plasma is a partially ionized gas expelling a variety of reactive oxygen and nitrogen species, which can be harnesses therapeutically. Plasmas and plasma-treated liquids have antitumor properties in vitro and in vivo. Yet, global response signatures to plasma treatment have not yet been identified. To this end, we screened eight human cancer cell lines to investigate effects of low-dose, tumor-static plasma-treated medium (PTM) on cellular activity, immune-modulatory properties, and transcriptional levels of 22 redox-related genes. With PTM, a moderate reduction of metabolic activity and modest modulation of chemokine/cytokine pattern and markers of immunogenic cell death was observed. Strikingly, the Nuclear factor (erythroid-derived 2)-like 2 (nrf2) target heme oxygenase 1 (hmox1) was upregulated in all cell lines 4 h post PTM-treatment. nrf2 was not changed, but its baseline expression inversely and significantly correlated with hmox1 expression after exposure to PTM. Besides awarding hmox1 a central role with plasma-derived oxidants, we present a transcriptional redox map of 22 targets and chemokine/cytokine secretion map of 13 targets across eight different human tumor cell lines of four tumor entities at baseline activity that are useful for future studies in this field.

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“…Recent extensive comparative studies on different biodosimetry approaches on the same irradiated cells underlines the necessity of employing a multiparametric approach to accomplish an accurate dose and risk estimation [8]. …”

Section: Plant Radiation Biodosimetermentioning

confidence: 99%

Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach

Nikitaki

Pavlopoulou

Holá

et al. 2017

Cancers

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The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR) pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM) in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR) and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana—based plant system monitoring the role of cancer-related DNA repair genes BRCA1, BARD1 and PARP1 in processing DNA lesions.

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Biomarkers of Ionizing Radiation Exposure: A Multiparametric Approach

Cited by 39 publications

References 27 publications

The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood

The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood

Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach

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