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 th...

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Autores principales:	Ion Udroiu, Antonella Sgura, Agnese Chendi, Lorenzo Lasagni, Marco Bertolini, Federica Fioroni, Vando Piccagli, Antonio Moramarco, Maria Grazia Romano, Luigi Fontana, Daniela D’Alessio, Vicente Bruzzaniti, Antonella Rosi, Sveva Grande, Alessandra Palma, Claudia Giliberti, Mauro Iori, Lorenzo Piergallini, Marco Sumini, Lorenzo Isolan, Giorgio Cucchi, Gaetano Compagnone, Lidia Strigari
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf38aac7fd6549e9baa72d4b56911938
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spelling	oai:doaj.org-article:bf38aac7fd6549e9baa72d4b569119382021-12-02T16:18:05ZDNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation10.1038/s41598-020-78383-22045-2322https://doaj.org/article/bf38aac7fd6549e9baa72d4b569119382020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78383-2https://doaj.org/toc/2045-2322Abstract 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.Ion UdroiuAntonella SguraAgnese ChendiLorenzo LasagniMarco BertoliniFederica FioroniVando PiccagliAntonio MoramarcoMaria Grazia RomanoLuigi FontanaDaniela D’AlessioVicente BruzzanitiAntonella RosiSveva GrandeAlessandra PalmaClaudia GilibertiMauro IoriLorenzo PiergalliniMarco SuminiLorenzo IsolanGiorgio CucchiGaetano CompagnoneLidia StrigariNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ion Udroiu Antonella Sgura Agnese Chendi Lorenzo Lasagni Marco Bertolini Federica Fioroni Vando Piccagli Antonio Moramarco Maria Grazia Romano Luigi Fontana Daniela D’Alessio Vicente Bruzzaniti Antonella Rosi Sveva Grande Alessandra Palma Claudia Giliberti Mauro Iori Lorenzo Piergallini Marco Sumini Lorenzo Isolan Giorgio Cucchi Gaetano Compagnone Lidia Strigari DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation
description	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.
format	article
author	Ion Udroiu Antonella Sgura Agnese Chendi Lorenzo Lasagni Marco Bertolini Federica Fioroni Vando Piccagli Antonio Moramarco Maria Grazia Romano Luigi Fontana Daniela D’Alessio Vicente Bruzzaniti Antonella Rosi Sveva Grande Alessandra Palma Claudia Giliberti Mauro Iori Lorenzo Piergallini Marco Sumini Lorenzo Isolan Giorgio Cucchi Gaetano Compagnone Lidia Strigari
author_facet	Ion Udroiu Antonella Sgura Agnese Chendi Lorenzo Lasagni Marco Bertolini Federica Fioroni Vando Piccagli Antonio Moramarco Maria Grazia Romano Luigi Fontana Daniela D’Alessio Vicente Bruzzaniti Antonella Rosi Sveva Grande Alessandra Palma Claudia Giliberti Mauro Iori Lorenzo Piergallini Marco Sumini Lorenzo Isolan Giorgio Cucchi Gaetano Compagnone Lidia Strigari
author_sort	Ion Udroiu
title	DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation
title_short	DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation
title_full	DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation
title_fullStr	DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation
title_full_unstemmed	DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation
title_sort	dna damage in lens epithelial cells exposed to occupationally-relevant x-ray doses and role in cataract formation
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/bf38aac7fd6549e9baa72d4b56911938
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DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation

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