Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, United Kingdom.
Durham University, School of Biosciences, Durham, United Kingdom.
Radiat Res. 2022 Jan 1;197(1):57-66. doi: 10.1667/RADE-20-00266.1.
Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate. Here, we present the results of a long-term study of changes to lens opacity in male and female adult mice from a variety of different genetic (radiosensitive or radioresistant) backgrounds, including mutant strains Ercc2 and Ptch1, which were assumed to be susceptible to radiation-induced lens opacities. Mice received 0.5, 1 and 2 Gy 60Co gamma-ray irradiation at dose rates of 0.063 and 0.3 Gy min-1. Scheimpflug imaging was used to quantify lens opacification as an early indicator of cataract, with monthly observations taken postirradiation for an 18-month period in all strains apart from 129S2, which were observed for 12 months. Opacification of the lens was found to increase with time postirradiation (with age) for most mouse models, with ionizing radiation exposure increasing opacities further. Sex, dose, dose rate and genetic background were all found to be significant contributors to opacification; however, significant interactions were identified, which meant that the impact of these factors was strain dependent. Mean lens density increased with higher dose and dose rate in the presence of Ercc2 and Ptch1 mutations. This project was the first to focus on low (<1 Gy) dose, multiple dose rate, sex and strain effects in lens opacification, and clearly demonstrates the importance of these experimental factors in radiobiological investigations on the lens. The results provide insight into the effects of ionizing radiation on the lens as well as the need for further work in this area to underpin appropriate radiation protection legislation and guidance.
最近的流行病学发现和对历史数据的重新分析表明，与以前认为的相比，来自电离辐射的晶状体混浊可能在更低的剂量下诱导。这些观察结果导致 ICRP 建议降低职业性晶状体剂量限值，随后在欧盟成员国实施。欧盟 CONCERT LDLensRad 项目的启动是为了进一步了解电离辐射对晶状体的影响，并确定辐射诱导白内障涉及的机制以及剂量和剂量率的影响。在这里，我们展示了一项长期研究的结果，该研究旨在研究来自各种不同遗传（辐射敏感或辐射抗性）背景的雄性和雌性成年小鼠晶状体混浊的变化，包括突变株 Ercc2 和 Ptch1，这些突变株被认为易受辐射诱导的晶状体混浊影响。小鼠以 0.063 和 0.3 Gy min-1 的剂量率接受 0.5、1 和 2 Gy 60Co γ射线照射。Scheimpflug 成像用于量化晶状体混浊作为白内障的早期指标，除 129S2 外，所有品系在照射后 18 个月内每月进行观察，129S2 观察 12 个月。结果发现，在大多数小鼠模型中，晶状体混浊随辐照后时间（随年龄）而增加，电离辐射进一步增加了混浊度。性别、剂量、剂量率和遗传背景均被发现对混浊度有显著影响；然而，还确定了显著的相互作用，这意味着这些因素的影响取决于品系。在存在 Ercc2 和 Ptch1 突变的情况下，晶状体密度随着剂量和剂量率的增加而增加。该项目首次关注晶状体混浊的低（<1 Gy）剂量、多剂量率、性别和品系效应，清楚地表明了这些实验因素在晶状体放射生物学研究中的重要性。研究结果提供了对电离辐射对晶状体影响的深入了解，以及在该领域进一步工作的必要性，以支持适当的辐射保护立法和指导。
