title: Nonlinear Radiation-Induced Cataract Using the Radiosensitive Ptch1(+/-) Mouse Model.
abstract: While most of the evidence for radiation-induced late health effects relates to cancer, there has been increasing interest recently in the development of non-cancer diseases, including lens opacity, observed in populations exposed to low-dose radiation. In a recent study, we reported that mice heterozygous for the Patched1 (Ptch1) gene represented a novel and powerful animal model for this disorder, and a useful tool for investigating the mechanisms of radiogenic cataract development. Given the ongoing and considerable uncertainty in allowable lens dose levels and the existence of a threshold for the development of cataracts, we tested the effects of a decreasing range of radiation doses (2 Gy, 1 Gy and 0.5 Gy X rays) by irradiating groups of Ptch1(+/-) mice at 2 days of age. Our findings showed that at this dose range, acute exposure of this highly susceptible mouse model did not induce macroscopically detectable cataracts, and only the 2 Gy irradiated mice showed microscopic alterations of the lens. Molecular analyses performed to evaluate the induction of epithelial-mesenchymal transition (EMT) and subsequent fibrotic alterations in mouse lens cells also indicated the existence of a dose threshold for such effects in the mouse model used. The mechanisms of cataractogenesis remain unclear, and further experimental studies are essential to elucidate those mechanisms specific for cataract initiation and development after irradiation, as well as the underlying genetic factors controlling cataract susceptibility.
authors.affiliation: b   Department of Radiation Physics, Guglielmo Marconi University, Rome, Italy;
authors.forename: Ilaria
authors.initials: I
authors.lastname: De Stefano
authors.affiliation: b   Department of Radiation Physics, Guglielmo Marconi University, Rome, Italy;|c   Department of Sciences, Roma Tre University, Rome, Italy; and.
authors.forename: Paola
authors.initials: P
authors.lastname: Giardullo
authors.affiliation: a   Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy;
authors.forename: Barbara
authors.initials: B
authors.lastname: Tanno
authors.affiliation: a   Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy;
authors.forename: Simona
authors.initials: S
authors.lastname: Leonardi
authors.affiliation: a   Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy;
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pasquali
authors.affiliation: d   Department of Physics, University of Pavia, Pavia, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Babini
authors.affiliation: a   Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy;
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
authors.affiliation: a   Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy;
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Mancuso
mesh_terms: D000483:Alleles; D000818:Animals; D002386:Cataract / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D007908:Lens, Crystalline / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D017711:Nonlinear Dynamics; D000072081:Patched-1 Receptor / Q000172:deficiency* / Q000235:genetics; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011836:Radiation Tolerance
chemical_list: D000072081:Patched-1 Receptor