{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T10:30:46Z","timestamp":1793442646890,"version":"4.5.0"},"reference-count":41,"publisher":"Radiation Research Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2021,3,2]]},"abstract":"<jats:p>Epidemiological studies suggest an increased incidence and risk of cataract after low-dose (&lt;2 Gy) ionizing radiation exposures. However, the biological mechanism(s) of this process are not fully understood. DNA damage and repair are thought to have a contributing role in radiation-induced cataractogenesis. Recently we have reported an inverse dose-rate effect, as well as the low-dose response, of DNA damage and repair in lens epithelial cells (LECs). Here, we present further initial findings from two mutated strains (Ercc2+\/\u2013 and Ptch1+\/\u2013) of mice, both reportedly susceptible to radiation-induced cataract, and their DNA damage and repair response to low-dose and low-dose-rate gamma rays. Our results support the hypothesis that the lens epithelium responds differently to radiation than other tissues, with reported radiation susceptibility to DNA damage not necessarily translating to the LECs. Genetic predisposition and strain(s) of mice have a significant role in radiation-induced cataract susceptibility.<\/jats:p>","DOI":"10.1667\/rade-20-00264.1","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T03:20:49Z","timestamp":1641180049000},"page":"36-42","source":"Crossref","is-referenced-by-count":8,"title":["Radiation-induced DNA Damage and Repair in Lens Epithelial Cells of both Ptch1(+\/\u2013) and Ercc2(+\/\u2013) Mutated Mice"],"prefix":"10.1667","volume":"197","author":[{"given":"S. G. R.","family":"Barnard","sequence":"first","affiliation":[{"name":"Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"McCarron","sequence":"additional","affiliation":[{"name":"Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pazzaglia","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Pawliczek","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen GmbH - German Research Center for Environmental Health, Institute of Developmental Genetics, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Dalke","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen GmbH - German Research Center for Environmental Health, Institute of Developmental Genetics, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A.","family":"Ainsbury","sequence":"additional","affiliation":[{"name":"Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"5","doi-asserted-by":"crossref","unstructured":"SGR Barnard, R McCarron, J Moquet, et al.  \"Sci Rep.\"  9, \"Inverse dose-rate effect of ionising radiation on residual 53BP1 foci in the eye lens.\" 10418 (2019)","DOI":"10.1038\/s41598-019-46893-3"},{"key":"23","doi-asserted-by":"publisher","unstructured":"K Rothkamm, S Barnard, J Moquet, et al.  \"Environ Mol Mutagen.\"  56, \"DNA damage foci: Meaning and significance.\" 491 (2015)","DOI":"10.1002\/em.21944"},{"key":"10","doi-asserted-by":"crossref","unstructured":"MP Little, CM Kitahara, EK Cahoon, et al.  \"Eur J Epidemiol.\"  33, \"Occupational radiation exposure and risk of cataract incidence in a cohort of US radiologic technologists.\" 1179 (2018)","DOI":"10.1007\/s10654-018-0435-3"},{"key":"1","doi-asserted-by":"crossref","unstructured":"EA Ainsbury, SD Bouffler, W Dorr, et al.  \"Radiat Res.\"  172, \"Radiation cataractogenesis: a review of recent studies.\" 1 (2009)","DOI":"10.1667\/RR1688.1"},{"key":"15","doi-asserted-by":"crossref","unstructured":"I de Stefano, B Tanno, P Giardullo, et al.  \"Am J Pathol.\"  185, \"The Patched 1 tumor-suppressor gene protects the mouse lens from spontaneous and radiation-induced cataract.\" 85 (2015)","DOI":"10.1016\/j.ajpath.2014.09.019"},{"key":"12","doi-asserted-by":"crossref","unstructured":"S Kunze, C Dalke, H Fuchs, et al.  \"Plos One.\"  10, \"New mutation in the mouse Xpd\/Ercc2 gene leads to recessive cataracts.\" e0125304 (2015)","DOI":"10.1371\/journal.pone.0125304"},{"key":"2","doi-asserted-by":"crossref","unstructured":"EA Ainsbury, S Barnard, S Bright, et al.  \"Mutat Res.\"  770, \"Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.\" 238 (2016)","DOI":"10.1016\/j.mrrev.2016.07.010"},{"key":"27","doi-asserted-by":"crossref","unstructured":"NJ Kleiman, J David, CD Elliston, et al.  \"Radiat Res.\"  168, \"Mrad9 and atm haploinsufficiency enhance spontaneous and X-ray-induced cataractogenesis in mice.\" 567 (2007)","DOI":"10.1667\/rr1122.1"},{"key":"13","doi-asserted-by":"crossref","unstructured":"I De Stefano, P Giardullo, B Tanno, et al.  \"Radiat Res.\"  186, \"Nonlinear radiation-induced cataract using the radiosensitive Ptch1(+\/\u2013) mouse model.\" 315 (2016)","DOI":"10.1667\/RR14440.1"},{"key":"41","doi-asserted-by":"crossref","unstructured":"S Pazzaglia, M Mancuso, MJ Atkinson, et al.  \"Oncogene.\"  21, \"High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice.\" 7580 (2002)","DOI":"10.1038\/sj.onc.1205973"},{"key":"3","doi-asserted-by":"crossref","unstructured":"A Uwineza, AA Kalligeraki, N Hamada, et al.  \"Mutat Res.\"  779, \"Cataractogenic load \u2013 a concept to study the contribution of ionizing radiation to accelerated aging in the eye lens.\" 68 (2019)","DOI":"10.1016\/j.mrrev.2019.02.004"},{"key":"4","doi-asserted-by":"crossref","unstructured":"K Bannik, U Rossler, T Faus-Kessler, et al.  \"Radiat Environ Biophys.\"  52, \"Are mouse lens epithelial cells more sensitive to gamma-irradiation than lymphocytes?\" 279 (2013)","DOI":"10.1007\/s00411-012-0451-8"},{"key":"6","doi-asserted-by":"crossref","unstructured":"SGR Barnard, J Moquet, S Lloyd, et al.  \"Int J Radiat Biol.\"  94, \"Dotting the eyes: mouse strain dependency of the lens epithelium to low dose radiation-induced DNA damage.\" 1116 (2018)","DOI":"10.1080\/09553002.2018.1532609"},{"key":"7","doi-asserted-by":"crossref","unstructured":"E Markiewicz, S Barnard, J Haines, et al.  \"Open Biol.\"  5, \"Nonlinear ionizing radiation-induced changes in eye lens cell proliferation, cyclin D1 expression and lens shape.\" 150011 (2015)","DOI":"10.1098\/rsob.150011"},{"key":"8","unstructured":"EJ. Hall,  \"Radiobiology for the radiologist.\"  (1973)"},{"key":"9","doi-asserted-by":"crossref","unstructured":"N. Hamada,  \"Int J Radiat Biol.\"  93, \"Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.\" 1024 (2017)","DOI":"10.1080\/09553002.2016.1266407"},{"key":"11","doi-asserted-by":"crossref","unstructured":"Y Wang, J Zhang, J Wu, et al.  \"Exp Mol Pathol.\"  102, \"Expression of DNA repair genes in lens cortex of age-related cortical cataract.\" 219 (2017)","DOI":"10.1016\/j.yexmp.2017.02.006"},{"key":"14","doi-asserted-by":"crossref","unstructured":"X Qi  and X Li  \"Trends Biochem Sci.\"  45, \"Mechanistic insights into the generation and transduction of hedgehog signaling.\" 397 (2020)","DOI":"10.1016\/j.tibs.2020.01.006"},{"key":"16","doi-asserted-by":"crossref","unstructured":"A Vulin, M Sedkaoui, S Moratille, et al.  \"Int J Radiat Oncol Biol Phys.\"  102, \"Severe PATCHED1 deficiency in cancer-prone gorlin patient cells results in intrinsic radiosensitivity.\" 417 (2018)","DOI":"10.1016\/j.ijrobp.2018.05.057"},{"key":"17","doi-asserted-by":"crossref","unstructured":"T Revenco, G Lapouge, V Moers, et al.  \"Stem Cells.\"  35, \"Low dose radiation causes skin cancer in mice and has a differential effect on distinct epidermal stem cells.\" 1355 (2017)","DOI":"10.1002\/stem.2571"},{"key":"18","doi-asserted-by":"crossref","unstructured":"D Ferri, D Orioli, E Botta,  \"Clin Genet.\"  97, \"Heterogeneity and overlaps in nucleotide excision repair disorders.\" 12 (2020)","DOI":"10.1111\/cge.13545"},{"key":"19","doi-asserted-by":"crossref","unstructured":"LH. Thompson,  \"Mutat Res.\"  247, \"Properties and applications of human DNA repair genes.\" 213 (1991)","DOI":"10.1016\/0027-5107(91)90017-I"},{"key":"20","doi-asserted-by":"crossref","unstructured":"C Dalke, F Neff, SK Bains, et al.  \"Radiat Environ Biophys.\"  57, \"Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial study with special focus on cataract risk.\" 99 (2018)","DOI":"10.1007\/s00411-017-0728-z"},{"key":"21","doi-asserted-by":"crossref","unstructured":"LK Lerner, NC Moreno, CRR Rocha, et al.  \"Mutagenesis.\"  34, \"XPD\/ERCC2 mutations interfere in cellular responses to oxidative stress.\" 341 (2019)","DOI":"10.1093\/mutage\/gez020"},{"key":"22","doi-asserted-by":"crossref","unstructured":"N Tuteja  and R Tuteja  \"Crit Rev Biochem Mol Biol.\"  36, \"Unraveling DNA repair in human: molecular mechanisms and consequences of repair defect.\" 261 (2001)","DOI":"10.1080\/20014091074192"},{"key":"24","doi-asserted-by":"crossref","unstructured":"MD Martin, DB Danahy, SM Hartwig, et al.  \"Front Immunol.\"  8, \"Revealing the complexity in CD8 T cell responses to infection in inbred C57B\/6 versus outbred swiss mice.\" 1527 (2017)","DOI":"10.3389\/fimmu.2017.01527"},{"key":"25","doi-asserted-by":"crossref","unstructured":"E Carreras, M Velasco de Andres, M Orta-Mascaro, et al.  \"Cell Microbiol.\"  21, \"Discordant susceptibility of inbred C57BL\/6 versus outbred CD1 mice to experimental fungal sepsis.\" e12995 (2019)","DOI":"10.1111\/cmi.12995"},{"key":"26","doi-asserted-by":"crossref","unstructured":"N Hamada  and Y Fujimichi  \"Cancer Lett.\"  368, \"Role of carcinogenesis related mechanisms in cataractogenesis and its implications for ionizing radiation cataractogenesis.\" 262 (2015)","DOI":"10.1016\/j.canlet.2015.02.017"},{"key":"28","doi-asserted-by":"crossref","unstructured":"BV Worgul, L Smilenov, DJ Brenner, et al.  \"Proc Natl Acad Sci U S A.\"  99, \"Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts.\" 9836 (2002)","DOI":"10.1073\/pnas.162349699"},{"key":"29","doi-asserted-by":"crossref","unstructured":"BV Worgul, L Smilenov, DJ Brenner, et al.  \"Adv Space Res.\"  35, \"Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes.\" 254 (2005)","DOI":"10.1016\/j.asr.2005.01.030"},{"key":"30","doi-asserted-by":"crossref","unstructured":"M Fujimoto, H Izu, K Seki, et al.  \"EMBO J.\"  23, \"HSF4 is required for normal cell growth and differentiation during mouse lens development.\" 4297 (2004)","DOI":"10.1038\/sj.emboj.7600435"},{"key":"31","doi-asserted-by":"crossref","unstructured":"L Bu, Y Jin, Y Shi, et al.  \"Nat Genet.\"  31, \"Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract.\" 276 (2002)","DOI":"10.1038\/ng921"},{"key":"32","doi-asserted-by":"crossref","unstructured":"Y Fujimichi  and N Hamada  \"PLoS One.\"  9, \"Ionizing irradiation not only inactivates clonogenic potential in primary normal human diploid lens epithelial cells but also stimulates cell proliferation in a subset of this population.\" e98154 (2014)","DOI":"10.1371\/journal.pone.0098154"},{"key":"33","doi-asserted-by":"crossref","unstructured":"NJ Kleiman  and A Spector  \"Curr Eye Res.\"  12, \"DNA single strand breaks in human lens epithelial cells from patients with cataract.\" 423 (1993)","DOI":"10.3109\/02713689309024624"},{"key":"34","doi-asserted-by":"crossref","unstructured":"OD. Scharer,  \"Cold Spring Harb Perspect Biol.\"  5, \"Nucleotide excision repair in eukaryotes.\" a012609 (2013)","DOI":"10.1101\/cshperspect.a012609"},{"key":"35","doi-asserted-by":"crossref","unstructured":"Q Li, AW Damish, Z Frazier, et al.  \"Clin Cancer Res.\"  25, \"ERCC2 helicase domain mutations confer nucleotide excision repair deficiency and drive cisplatin sensitivity in muscle-invasive bladder cancer.\" 977 (2019)","DOI":"10.1158\/1078-0432.CCR-18-1001"},{"key":"36","doi-asserted-by":"crossref","unstructured":"YZ Song, MN Duan, YY Zhang, et al.  \"Radiat Oncol.\"  10, \"ERCC2 polymorphisms and radiation-induced adverse effects on normal tissue: systematic review with meta-analysis and trial sequential analysis.\" 247 (2015)","DOI":"10.1186\/s13014-015-0558-6"},{"key":"37","doi-asserted-by":"crossref","unstructured":"Y Wang, F Li, G Zhang, et al.  \"Clin Epigenetics.\"  8, \"Ultraviolet-B induces ERCC6 repression in lens epithelium cells of age-related nuclear cataract through coordinated DNA hypermethylation and histone deacetylation.\" 62 (2016)","DOI":"10.1186\/s13148-016-0229-y"},{"key":"38","doi-asserted-by":"crossref","unstructured":"Z Choudhry, AA Rikani, AM Choudhry, et al.  \"Ann Neurosci.\"  21, \"Sonic hedgehog signalling pathway: a complex network.\" 28 (2014)","DOI":"10.5214\/ans.0972.7531.210109"},{"key":"39","doi-asserted-by":"crossref","unstructured":"E Meng, A Hanna, RS Samant, et al.  \"Cancers.\"  7, \"The impact of Hedgehog signaling pathway on DNA repair mechanisms in human cancer.\" 1333 (2015)","DOI":"10.3390\/cancers7030839"},{"key":"40","doi-asserted-by":"crossref","unstructured":"M Tanori, E Pasquali, S Leonardi, et al.  \"Oncogene.\"  30, \"Opposite modifying effects of HR and NHEJ deficiency on cancer risk in Ptc1 heterozygous mouse cerebellum.\" 4740 (2011)","DOI":"10.1038\/onc.2011.178"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T09:40:30Z","timestamp":1793439630000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-197\/issue-1\/RADE-20-00264.1\/Radiation-induced-DNA-Damage-and-Repair-in-Lens-Epithelial-Cells\/10.1667\/RADE-20-00264.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,2]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-20-00264.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,2]]}}}