DNA damage-associated biomarkers in studying individual sensitivity to low-dose radiation from cardiovascular imaging

Lee, Won Hee; Nguyen, Patricia K.; Fleischmann, Dominik; Wu, Joseph C.

doi:10.1093/eurheartj/ehw206

Cited by 27 publications

(17 citation statements)

References 96 publications

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“…These include dicentric chromosomes [ 64 ], micronuclei [ 65 ] and γН2АХ foci [ 66 ]. However, it is not yet clear whether these are good prediction markers for delayed effects [ 67 ]. Physiological systemic changes, such as cellular aging or senescence, may provide a better reference for evaluating a long-term change as a result of low-dose exposure.…”

Section: Discussionmentioning

confidence: 99%

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

Pustovalova

Астрелина

Grekhova

et al. 2017

Aging

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Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γН2АХ foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γН2АХ foci still present at 24 h. Notably, these low dose induced residual γН2АХ foci were not co-localized with рАТМ foci and were observed predominantly in the proliferating Кi67 positive (Кi67+) cells. The number of γН2АХ foci and the fraction of nonproliferating (Кi67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γН2АХ foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AХ foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.

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Section: Discussionmentioning

confidence: 99%

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

Pustovalova

Астрелина

Grekhova

et al. 2017

Aging

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“…13,14 Double-stranded DNA breaks induced by ionizing radiation lead to phosphorylation of the histone protein H2AX to form γ-H2AX, with the levels of γ-H2AX in the cell peaking half an hour after exposure to radiation. [15][16][17] During the acute phase of exposure, DNA damage in lymphocytes also results in induction of a damage sensor known as the Mre11-Rad50-Nbs1 complex, which causes rapid phosphorylation of ataxia telangiectasia mutated (ATM) protein.…”

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confidence: 99%

“…27 Emerging data suggest, however, that there is variability in tissue response to radiation, the safe threshold may vary between individuals, and the risk relationship is not linear. 14,28 The present study aimed to (1) study the biological effect of radiation exposure in operators by measuring pATM and γ-H2AX expression in circulating lymphocytes after EVAR, (2) examine individual operator sensitivity to radiation exposure using γ-H2AX levels as a biomarker, and (3) evaluate the protective effect of wearing lower leg lead shielding.…”

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confidence: 99%

Radiation Induced DNA Damage in Operators Performing Endovascular Aortic Repair

El-Sayed¹,

Patel²,

Cho³

et al. 2018

Journal of Vascular Surgery

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BACKGROUND:Radiation exposure during fluoroscopically guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR. METHODS:Expression of the DNA damage/repair marker, γ-H2AX and DNA damage response marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infrarenal, branched, and fenestrated) and open aortic repair using flow cytometry. These markers were separately measured in the same operators but this time wearing leg lead shielding in addition to upper body protection and compared with those operating with unprotected legs. Susceptibility to radiation damage was determined by irradiating operators' blood in vitro.RESULTS: γ-H2AX and pATM levels increased significantly in operators immediately after branched endovascular aortic repair/fenestrated endovascular aortic repair (P<0.0003 for both). Only pATM levels increased after infrarenal endovascular aortic repair (P<0.04). Expression of both markers fell to baseline in operators after 24 hours (P<0.003 for both). There was no change in γ-H2AX or pATM expression after open repair. Leg protection abrogated γ-H2AX and pATM response after branched endovascular aortic repair/fenestrated endovascular aortic repair. The expression of γ-H2AX varied significantly when operators' blood was exposed to the same radiation dose in vitro (P<0.0001).CONCLUSIONS: This is the first study to detect an acute DNA damage response in operators performing fluoroscopically guided aortic procedures and highlights the protective effect of leg shielding. Defining the relationship between this response and cancer risk may better inform safe levels of chronic low-dose radiation exposure. 1,2 The growing number and complexity of procedures means that interventionists are exposed to higher amounts of radiation, a subject that is becoming increasingly topical. Radiation-Induced3-7 A recently published 15-year follow-up study of the EVAR trial, comparing endovascular and open aortic repair, reported an increased incidence of malignancy in patients treated by EVAR. 8 There is, rightly so, a significant focus currently on reducing the patients' exposure to radiation, but mounting evidence suggests that recurrent lowdose exposure to the practitioner is equally as important. Robust data collection to assess the risks posed to the interventionist is in its infancy, but a number of studies suggest a link to adverse health effects, including a higher risk of posterior subcapsular lens changes and malignancy.9-11 One recent study found a higher incidence of malignancy, including brain cancer, breast cancer, and melanoma, in interventionists who performed fluoroscopically guided procedures compared with those who had never performed these.12 A better understanding of the hazards of occupational radiation exposure requires sensitive tools to measure exposure at an individu...

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“…IR induces DNA damage, to which cells respond by activation of DDR pathways, enabling repair of the genotoxic lesions. Circulating lymphocytes are particularly sensitive to radiation and may therefore offer the opportunity to study biological effects of low-dose exposure 17. Therefore, DNA damage and its repair were assessed in peripheral blood samples of subjects occupationally exposed to IR and compared with a control population.…”

Section: Discussionmentioning

confidence: 99%