High and low dose responses of transcriptional biomarkers in<i>ex vivo</i>X-irradiated human blood

Manning, Grainne; Kabacik, Sylwia; Finnon, Paul; Bouffler, Simon; Badie, Christophe

doi:10.3109/09553002.2013.769694

Cited by 104 publications

(128 citation statements)

References 38 publications

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“…FAS-AS1 has been identified by Yan et al (35) as an antisense transcript of the FAS gene and the authors proposed that it might protect T lymphocytes from FASmediated apoptosis. We have previously shown a consistent up-regulation of FAS in C1 and C2 (15) and there is probably a fine balance between the pro-and anti-apoptotic transcripts deciding on the fate of an irradiated cell. To our knowledge, this is the first study of FAS-AS1 being upregulated by ionizing radiation, but we also expect or predict that there are other radiation-responsive lncRNAs awaiting discovery.…”

Section: Figmentioning

confidence: 77%

“…In addition, we investigated the response to radiation of two lncRNAs, the expression of which was reported to be altered by radiomimetic drug treatment: TP53TG1 (38) and PANDAR (41), and also a FAS antisense RNA 1 (FAS-AS1), which is transcribed in anti-sense orientation to the FAS gene (35), a well known radiation-responsive transcript (15).…”

Section: Temporal Response To Ionizing Radiationmentioning

confidence: 99%

“…With the development of microarray technology that enables screening of hundreds of genes simultaneously (5), it became clear that many more genes are modulated in response to radiation exposure (6-13), mostly in a TP53-dependent manner. Gene expression changes after exposure to radiation are now well documented in human blood (14), even after low-dose exposures (15).…”

Section: Introductionmentioning

confidence: 99%

“…As we have recently shown, for some genes there is significant variability in the transcriptional response to radiation within the healthy population (15). There are also individuals in certain populations, such as ataxia-telangiectasia (AT) patients, who display a characteristic phenotype, including hypersensitivity to ionizing radiation and chromosomal instability (51).…”

Section: Introductionmentioning

confidence: 99%

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Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

et al. 2015

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Section: Figmentioning

confidence: 77%

Section: Temporal Response To Ionizing Radiationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

et al. 2015

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“…A linear dose-reponse has been observed by reverse transcriptase-QPCR from doses 1-3 Gy [47] and 0.5-4 Gy [48]. A recent study by Manning et al [49] has illustrated the potential of gene expression to be used in the triage of patients by using dose-response curves to identify blood samples exposed to a low (5-100 mGy) or high (0.5-4 Gy) dose of irradiation. Although these results are encouraging, larger population studies must be carried out to assess the variation in response for different genes.…”

Section: Gene Expression Techniquesmentioning

confidence: 99%

Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

Manning

Rothkamm²

2013

BJR

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Diagnostic and therapeutic radiation technology has developed dramatically in recent years, and its use has increased significantly, bringing clinical benefit. The use of diagnostic radiology has become widespread in modern society, particularly in paediatrics where the clinical benefit needs to be balanced with the risk of leukaemia and brain cancer increasing after exposure to low doses of radiation. With improving long-term survival rates of radiotherapy patients and the ever-increasing use of diagnostic and interventional radiology procedures, concern has risen over the long-term risks and side effects from such treatments. Biomarker development in radiology and radiotherapy has progressed significantly in recent years to investigate the effects of such use and optimise treatment. Recent biomarker development has focused on improving the limitations of established techniques by the use of automation, increasing sensitivity and developing novel biomarkers capable of quicker results. The effect of low-dose exposure (0-100 mGy) used in radiology, which is increasingly linked to cancer incidences, is being investigated, as some recent research challenges the linear-no-threshold model. Radiotherapy biomarkers are focused on identifying radiosensitive patients, determining the treatment-associated risk and allowing for a tailored and more successful treatment of cancer patients. For biomarkers in any of these areas to be successfully developed, stringent criteria must be applied in techniques and analysis of data to reduce variation among reports and allow data sets to be accurately compared. Newly developed biomarkers can then be used in combination with the established techniques to better understand and quantify the individual biological response to exposures associated with radiology tests and to personalise treatment plans for patients.

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Increased circulating cell‐free DNA levels and mtDNA fragments in interventional cardiologists occupationally exposed to low levels of ionizing radiation

Borghini

Mercuri

Turchi

et al. 2014

Environ and Mol Mutagen

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Circulating cell-free DNA (ccf-DNA) and mtDNA (ccf-mtDNA) have often been used as indicators of cell death and tissue damage in acute and chronic disorders, but little is known about changes in ccf-DNA and ccf-mtDNA concentrations following radiation exposure. The aim of the study was to investigate the impact of chronic low-dose radiation exposure on serum ccf-DNA levels and ccf-mtDNA fragments (mtDNA-79 and mtDNA-230) of interventional cardiologists working in high-volume cardiac catheterization laboratory to assess their possible role as useful radiation biomarkers. We enrolled 50 interventional cardiologists (26 males; age = 48.4 ± 10 years) and 50 age- and gender-matched unexposed controls (27 males; age = 47.6 ± 8.3 years). Quant-iT™ dsDNA High-Sensitivity assay was used to measure circulating ccf-DNA isolated from serum samples. Quantitative analysis of mtDNA fragments was performed by real-time PCR. No significant relationships were found between ccf-DNA and ccf-mtDNA, and age, gender, smoking, or other clinical parameters. Ccf-DNA levels (44.2 ± 31.1 vs. 30.6 ± 19.2 ng/ml, P = 0.013), ccf-mtDNA-79 (2.6 ± 2.1 vs. 1.1 ± 0.8, P < 0.01), and ccf-mtDNA-230 copies (2.0 ± 1.8 vs. 1.04 ± 0.9, P = 0.02) were significantly higher in interventional cardiologists compared with the non-exposed group. In a subset (n = 15) of interventional cardiologists with a reliable reconstruction of cumulative professional exposure (59.7 ± 48.4 mSv; range: 1.4-182 mS), ccf-DNA (53.2 ± 41.3 vs. 36.4 ± 22.9 and 32.2 ± 20.5, P = 0.08), mtDNA-79 (2.4 ± 2.1 vs. 2.03 ± 1.7 and 1.09 ± 0.82, P = 0.05), and mtDNA-230 (2.0 ± 2.2 vs. 1.5 ± 1.4 and 1.04 ± 0.9, P = 0.09) tended to be significantly increased in high-exposure subjects compared with both low-exposure interventional cardiologists and controls. Our results provide evidence for a possible role of circulating DNA as a relevant biomarker of cellular damage induced by exposure to chronic low-dose radiation.

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High and low dose responses of transcriptional biomarkers inex vivoX-irradiated human blood

Abstract: These findings identify genes that fulfill some of the requirements of a good exposure biomarker even at low doses, such as sensitivity, reproducibility and simple proportionality with dose.

Cited by 104 publications

References 38 publications

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

Time, Dose and Ataxia Telangiectasia Mutated (ATM) Status Dependency of Coding and Noncoding RNA Expression after Ionizing Radiation Exposure

Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

Increased circulating cell‐free DNA levels and mtDNA fragments in interventional cardiologists occupationally exposed to low levels of ionizing radiation

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