DNA damage response in workers exposed to low-dose ionising radiation

Gaetani, Simona; Monaco, Francesca Roversi; Bracci, Massimo; Ciarapica, Veronica; Impollonia, Giulia; Valentino, Matteo; Tomasetti, Marco; Santarelli, Lory; Amati, Monica

doi:10.1136/oemed-2018-105094

Cited by 26 publications

(19 citation statements)

References 32 publications

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“…However, this finding can be supported by something known as “radiation hormesis model,” which assumes that adaptive/protective mechanisms can be stimulated over time by low-dose radiation and that they can prevent the occurrence of mutations in the cells (Vaiserman, 2010). Evidence of hormesis throughout defined low-dose IR ranges was previously described (Crump et al, 2012; Gaetani et al, 2018; Qian et al, 2016; Sahin et al, 2009; Sakly et al, 2012; Ündeǧer et al, 1999).…”

Section: Discussionmentioning

confidence: 76%

“…Fortunately, the application of principles of radiological protection has decreased the levels of exposure to IR in these workers, and they are usually below the limit of 20 mSv/year (Dobrzyńska et al, 2014; International Commission on Radiological Protection, 2007). However, several studies have shown increased genetic damage, such as frequency of micronuclei, chromosomal aberrations, and DNA strand breaks, after chronic exposure to low doses of IR from diagnostic X-ray and nuclear medicine areas (Bouraoui et al, 2013; Cardoso et al, 2001; Dobrzyńska et al, 2014; Doukali et al, 2017a; Gaetani et al, 2018; Garaj-Vrhovac and Kopjar, 2003; Güerci et al, 2006; Kopjar and Garaj-Vrhovac, 2005; Kumar et al, 2015; Sari-Minodier et al, 2007; Wojewódzka et al, 1998; Zakeri and Hirobe, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Genotoxic risk in health-care professionals occupationally exposed to low doses of ionizing radiation

et al. 2020

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The purpose of this study was to evaluate the potential influence of occupational ionizing radiation (IR) exposure on health professionals, assessing DNA damage using the comet and micronucleus (MN) assays and analyzing relative risks, correlations, and associated factors between outcomes and socioeconomic and lifestyle factors. Blood and buccal samples were collected from 36 workers, who actively participated in an imaging sector of a hospital, who were either exposed to IR directly or indirectly (9 internal control and 27 exposed), and 27 individuals living in the same city but with no occupational exposure (external control, unexposed/healthy). All radiation dosages performed on the 36 workers were less than 20 mSv/y, not exceeding the effective dose limit for occupational exposure. A questionnaire identified socioeconomic and lifestyle factors associated with the outcomes. The results of the MN assay showed a significant difference between both internal control and the exposed group when compared to the external control. For the comet assay, there were significant differences between the percent of tail DNA of the exposed group and external controls, but no difference was found between the exposed group and internal controls. Relative risk associations were found in time of exposure, hours worked per week, and perceived stress. Correlations were found between the outcomes and age, consumption of alcohol, and frequencies of X-rays during life. Variables that showed to be significant in the adjusted analysis were skin color and recent exposure to radiation. Albeit limited, the findings of this study suggest genotoxicity in both blood and buccal mucosa cells of workers exposed directly or indirectly to IR and that lifestyle and socioeconomic factors are associated and correlated with the risk of developing these outcomes.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Genotoxic risk in health-care professionals occupationally exposed to low doses of ionizing radiation

et al. 2020

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“…Nagle et al 421 reported that low-dose irradiation of high-density murine and human glandular stem cells represented a dose threshold for DNA damage repair activation, leading to lowdose hyperradiosensitivity. Gaetani et al 422 investigated the effects of low-dose IR on DNA damage in circulating cells of occupationally exposed workers; the results showed that among workers with low-dose IR exposure, DNA repair activity was increased, and moreover, workers with cancer cases in their family history showed significantly reduced 8oxoguanine glycosylase 1-dependent DNA repair activity compared with those workers without any family history of cancer. Although the effects of low-dose radiation on DNA have attracted increasing attention over the past decade, the molecular mechanisms, biomarkers, and possible clinical applicability require further investigation.…”

Section: Challenges For Ir-induced Signal Transduction and Targeted Therapymentioning

confidence: 99%

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Huang

Zhou

2020

Sig Transduct Target Ther

676

457

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Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia-telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.

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“…MN formation is considered a reliable biomarker of exposure to clastogenic and aneugenic agents, including IR (26)(27)(28). In addition to MN, other cytogenetic tests, including the comet assay (29)(30)(31)(32) and chromosome aberration assays (33)(34)(35)(36), have confirmed the association between genotoxicity and low-dose radiation exposure.…”

Section: Resultsmentioning

confidence: 99%

Absence of mutations in the human interferon alpha-2b gene in workers chronically exposed to ionising radiation

Botbayev

Ravegnini

Sammarini

et al. 2019

Archives of Industrial Hygiene and Toxicology

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Individuals chronically exposed to low-level ionising radiation (IR) run the risk of harmful and long-term adverse health effects, including gene mutations and cancer development. The search for reliable biomarkers of IR exposure in human population is still of great interest, as they may have a great implementation potential for the surveillance of occupationally exposed individuals. In this context, and considering previous literature, this study aimed to identify mutations in the human interferon alpha-2b (hIFNα-2b) as a potential biomarker of occupational chronic low-dose IR exposure linking low-IR exposure to the effects on haematopoiesis and reduced immunity. The analysis was performed in the genomic DNA of 51 uranium miners and 38 controls from Kazakhstan, and in 21 medical radiology workers and 21 controls from Italy. hIFNα-2b gene mutations were analysed with the real-time polymerase chain reaction (PCR) or Sanger sequencing. However, none of the investigated workers had the hIFNα-2b mutation. This finding highlights the need for further research to identify biomarkers for early detection of health effects associated with chronic low-dose IR exposure.

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DNA damage response in workers exposed to low-dose ionising radiation

Abstract: Our results indicate that chronic exposure to a low dose of IR in occupational settings induces DDR in exposed subjects and may be mutagenic in workers with family history of cancer, suggesting that periodic surveillance might be advisable, along with exposure monitoring.

Cited by 26 publications

References 32 publications

Genotoxic risk in health-care professionals occupationally exposed to low doses of ionizing radiation

Genotoxic risk in health-care professionals occupationally exposed to low doses of ionizing radiation

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Absence of mutations in the human interferon alpha-2b gene in workers chronically exposed to ionising radiation

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