The use of cytogenetic and molecular endpoints as biomarkers of low dose radiation exposure in interventional cardiology

The extensive use of low doses of ionizing radiation (≤100 mSv) for diagnostic and therapeutic purposes increases concern on the radiation safety of both patients and physicians. Ionizing radiation exposures have almost doubled in the last decade, mainly due to the rise in medical diagnostic and therapeutic interventions, which are responsible for approximately 40% of the cumulative effective dose of radiation to the population. Despite the wide use of low-ionizing-radiation doses and the recent evidence that cancer risk may increase even at lower doses (between 50-100 mSv)  the effects of such exposures in patients exposed to cardiac images and interventional cardiology procedures remain unclear.

According to epidemiologic literature, the impact of low doses are hampered by limited statistical power at radiation levels of less than 100 mSv, even for very large studies. Alternatively, the investigation of the radiation-induced effects after exposure to low doses could be carried out with radiobiological data. The present study’s objective is to determine the biological effects of low doses in patients exposed to ionizing radiation during interventional cardiology procedures by using several biomarkers and the correlation of these doses with the potential development of cancer.

The 1st  objective involves the use of molecular and cytogenetic biomarkers to investigate the biological effects delivered to patients after their exposure to cardiovascular procedures at Onassis Cardiac Surgery Centre. Blood samples (6-7 ml) from  patients who undergo ordinary interventional cardiology procedures, such as Coronary Angiography, Percutaneous Transluminal Coronary Angioplasty, and ablation are collected directly before, and immediately after the end of the procedure and incubated in heparin-containing vials for each time interval. The induction and repair of DSBs is visualized and quantified by using the highly sensitive epigenetic biomarker γ-H2AX, a phosphorylated histone H2A variant. Chromosomal aberrations and micronuclei are both crucial predictors of the degree of radiation damage. The frequency of dicentric chromosomes and micronuclei is detected and is compared to the baseline.

Furthermore, the 2nd objective involves the potentiation of the unrepaired DSBs to induce asymmetric cell divisions and chromosomal instability, is tested by using the methodology of CB-iFISH that combines cytokinesis block mediated cell culturing with interphase Fluorescence in situ Hybridization (CB-iFISH) in human lymphocytes that are irradiated in vitro with low ionizing radiation doses. This combined methodology enables the visualization of centromeric regions in the micronuclei as well as the monitoring of the chemically-induced asymmetric cell divisions. The evaluation of the potential ability of the unrepaired radiation-induced DSBs to induce chromosomal instability and asymmetric cell division, will contribute in the research of radiobiology and radioprotection.

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