Assessment of DNA double‐strand breaks induced by intravascular iodinated contrast media following in vitro irradiation and in vivo, during paediatric cardiac catheterization

Abstract

Paediatric cardiac catheterizations may result in the administration of substantial amounts of iodinated contrast media and ionizing radiation. The aim of this work was to investigate the effect of iodinated contrast media in combination with in vitro and in vivo X-ray radiation on lymphocyte DNA. Six concentrations of iodine (15, 17.5, 30, 35, 45, and 52.5 mg of iodine per mL blood) represented volumes of iodinated contrast media used in the clinical setting. Blood obtained from healthy volunteers was mixed with iodinated contrast media and exposed to radiation doses commonly used in paediatric cardiac catheterizations (0 mGy, 70 mGy, 140 mGy, 250 mGy and 450 mGy). Control samples contained no iodine. For in vivo experimentation, pre and post blood samples were collected from children undergoing cardiac catheterization, receiving iodine concentrations of up to 51 mg of iodine per mL blood and radiation doses of up to 400 mGy. Fluorescence microscopy was performed to assess γH2AX-foci induction, which corresponded to the number of DNA double-strand breaks. The presence of iodine in vitro resulted in significant increases of DNA double-strand breaks beyond that induced by radiation for ≥ 17.5 mg/mL iodine to blood. The in vivo effects of contrast media on children undergoing cardiac catheterization resulted in a 19% increase in DNA double-strand breaks in children receiving an average concentration of 19 mg/mL iodine to blood. A larger investigation is required to provide further information of the potential benefit of lowering the amount of iodinated contrast media received during X-ray radiation investigations.

DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [68Ga]Ga-PSMA I&T

“…Many further studies used the γ-H2AX assay both ex vivo and in vivo for investigation of DNA damage in blood lymphocytes induced during CT examinations and, in particular, to investigate the effect of iodinated contrast agents [23,[29][30][31][32][33][34][35][36]. In agreement with the results of our ex vivo study, the majority of these studies report an increase of DNA damage in the contrast media-enhanced samples.…”

“…In agreement with the results of our ex vivo study, the majority of these studies report an increase of DNA damage in the contrast media-enhanced samples. Despite the findings in some of the ex vivo studies that this increase is only significant for high concentrations of the iodinated contrast agents used (up to 50 mg mL −1 ) or high radiation doses (up to 1 Gy) but not in a range that is clinically relevant for diagnostic procedures [30,34], many patient studies show that there is an 30 to 107% increase in DNA damage when contrast agents are applied compared to non-contrast enhanced examinations [31,32,[34][35][36].…”

The impact of iodinated contrast media on intravascular and extravascular absorbed doses in X-ray imaging: A microdosimetric analysis

“…For the model representing cells surrounded by interstitial fluid, the presence of extracellular iodine increased dose to cells (Table 6) The dose enhancement factors obtained in the current study were also compared to observed increases in blood cell damage foci (lymphocyte γH2AX, dicentrics and survival) reported in serval in vitro studies, cf. [18][19][20][21]. These damage foci were increased by an average factor of 1.28 for ρiI levels between 3.7 and 7.4 mg/ml (range: 0.8-1.7) thus similar to our DEFICM figures in the first 2-3 μm of the vessel wall (i.e.…”

“…As ICM do not appear to increase DNA damage when mixed with blood in the absence of irradiation [21,23,24], or are pre-irradiated before mixing [23], the observed increase in lymphocyte DNA damage appears to be mostly (if not entirely) dosimetric in nature. There is reasonably strong evidence that ionising radiation exposure increases the risk of cardiovascular disease (CVD), including among individuals receiving radiotherapy and those occupationally exposed [26,27].…”

Removal of scatter radiation in paediatric cardiac catheterisation: a randomised controlled clinical trial

“…Biomarkers of radiation exposure may also be used to assess the cellular effects of radiation exposure and have been encouraged by the United Nations Scientific Committee on the Effects of Atomic Radiation [18] . In particular the highly sensitive γH2AX assay has enabled the immunofluorescence of radiation-induced DNA double-strand breaks following ex vivo ionising radiation in isolated blood lymphocytes [19][20][21][22][23] . One of the earliest responses is the phosphorylation of the histone H2AX at serine 139 [24] .…”