DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation

Abstract

The current framework of radiological protection of occupational exposed medical workers reduced the eye-lens equivalent dose limit from 150 to 20 mSv per year requiring an accurate dosimetric evaluation and an increase understanding of radiation induced effects on Lens cells considering the typical scenario of occupational exposed medical operators. Indeed, it is widely accepted that genomic damage of Lens epithelial cells (LEC) is a key mechanism of cataractogenesis. However, the relationship between apoptosis and cataractogenesis is still controversial. In this study biological and physical data are combined to improve the understanding of radiation induced effects on LEC. To characterize the occupational exposure of medical workers during angiographic procedures an INNOVA 4100 (General Electric Healthcare) equipment was used (scenario A). Additional experiments were conducted using a research tube (scenario B). For both scenarios, the frequencies of binucleated cells, micronuclei, p21-positive cells were assessed with different doses and dose rates. A Monte-Carlo study was conducted using a model for the photon generation with the X-ray tubes and with the Petri dishes considering the two different scenarios (A and B) to reproduce the experimental conditions and validate the irradiation setups to the cells. The simulation results have been tallied using the Monte Carlo code MCNP6. The spectral characteristics of the different X-ray beams have been estimated. All irradiated samples showed frequencies of micronuclei and p21-positive cells higher than the unirradiated controls. Differences in frequencies increased with the delivered dose measured with Gafchromic films XR-RV3. The spectrum incident on eye lens and Petri, as estimated with MCNP6, was in good agreement in the scenario A (confirming the experimental setup), while the mean energy spectrum was higher in the scenario B. Nevertheless, the response of LEC seemed mainly related to the measured absorbed dose. No effects on viability were detected. Our results support the hypothesis that apoptosis is not responsible for cataract induced by low doses of X-ray (i.e. 25 mGy) while the induction of transient p21 may interfere with the disassembly of the nuclear envelop in differentiating LEC, leading to cataract formation. Further studies are needed to better clarify the relationship we suggested between DNA damage, transient p21 induction and the inability of LEC enucleation.

X-ray and DNA Damage: Limitations of the Dose as a Parameter for In Vitro Studies

“…In this way, we obtained X-rays with different photon energies but with the same dose rate and, vice versa, X-rays with different dose rates but with the same photon energy (Table 2). Spectra and dosimetry were conducted as reported in a previous work [24]. This cell line was chosen because following treatment with Cytochalasin-B (see Section 3.3), binucleated cells can be obtained with doses up to ≈3 Gy, whereas other cell lines (e.g., fibroblasts) are completely blocked at 2 Gy, showing no binucleated cells and thus making the micronucleus test unfeasible [19].…”

Staff eye lens dose in interventional radiology and cardiology in Finland

“…Lens doses exceeding 20 mSv/year [7,9] and even 50 mSv/year [5,10] have been reported, raising concerns that the current ICRP nominal lifetime threshold dose of 0.5 Gy for cataract induction [11] might be exceeded. Considering the increasing evidence for cataract formation at even lower doses than 0.5 Gy [12,13], estimation of eye lens dose of the most exposed workers should be a priority.…”

How direct measurements of worker eyes with a Scheimpflug camera can affect lensdose coefficients in interventional radiology

“…By way of caution, European directive 2013/59/Euratom [4] and ICRP 118 [1] proposed a new restrictive lensdose limit for exposed workers who use ionising radiation, changing the annual dose limit from 150 mSv to 20 mSv. This change has a strong impact on healthcare facilities, requiring them to evaluate the lens doses of exposed workers to a higher level of accuracy, especially in the field of interventional radiology [5][6][7][8].…”