This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

These findings demonstrate a dose dependent increased risk of posterior lens opacities for interventional cardiologists and nurses when radiation protection tools are not used. While study of a larger cohort is needed to confirm these findings, the results suggest ocular radio-protection should be utilized.

The lens of the eye is one of the most radiosensitive tissues in the body, and exposure of the lens to ionizing radiation can cause cataract. Cumulative X-ray doses to the lenses of interventional cardiologists and associated staff can be high. The International Commission on Radiological Protection recently noted considerable uncertainty concerning radiation risk to the lens. This study evaluated risk of radiation cataract after occupational exposure in interventional cardiology personnel. Comprehensive dilated slit-lamp examinations were performed in interventional cardiologists, associated workers and controls. Radiation exposures were estimated using experimental data from catheterization laboratories and answers to detailed questionnaires. A total of 116 exposed and 93 similarly aged nonexposed individuals were examined. The relative risk of posterior subcapsular opacities in interventional cardiologists compared to unexposed controls was 3.2 (38% compared to 12%; P < 0.005). A total of 21% of nurses and technicians had radiation-associated posterior lens changes typically associated with ionizing radiation exposure. Cumulative median values of lens doses were estimated at 6.0 Sv for cardiologists and 1.5 Sv for associated medical personnel. A significantly elevated incidence of radiation-associated lens changes in interventional cardiology workers indicates there is an urgent need to educate these professionals in radiation protection to reduce the likelihood of cataract.

Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cataracts eventually develop in 87% of ephrin-A5 KO mice. We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of ␤-catenin to N-cadherin. These results indicate that the Eph receptors and their ligands are critical regulators of lens development and maintenance.␤-catenin ͉ Eph receptor ͉ N-cadherin C ataract, or the opacification of the lens, is the leading cause of visual impairment and blindness worldwide (1). The molecular events underlying lens development and the processes by which the lens maintains transparency over a lifetime are unclear (2). In addition, the cellular and biochemical mechanisms underlying the pathological changes leading to cataract remain poorly understood.The lens is composed of a single layer of epithelial cells on the anterior surface, which, over a lifetime, divide and differentiate into the underlying lens fiber cells that comprise the bulk of the lens (3, 4). Initially during lens development, primary lens fiber cells differentiate and elongate from the posterior pole. In later embryogenesis and throughout life, secondary lens fiber cells differentiate from lens epithelial cells located at the equator. In cross section, the lens fiber cells resemble flattened hexagons with two broad and four short sides (3). These cells are organized in a highly ordered and closely packed manner, and interact through extensive intercellular adhesion complexes including gap and adherens junctions (5). Fiber cell gap junctions are composed of connexins (Cx) 46 and 50 (6), inactivation of which leads to the degeneration of the inner fiber cells and the development of cataract in mice (7,8). Mutations in human Cx genes have also been associated with cataractogenesis (9, 10). As the lens is completely enclosed by an acellular, avascular capsule, it is believed that these cell-cell junctions are critical for providing nutrient transport, removal of metabolic wastes, and maintenance of homeostasis (11,12). In addition to gap junctions, widespread adherens junctions containing N-cadherin and its associated protein ␤-catenin exist between lens fiber cells (13-16), and may play important roles in lens development and function.Although cell-cell interaction is critical for maintaining lens transparency, little is known about the molecular mechanisms underlying these interactions. We have identified an unexpected regulator of lens fiber cell-cell interaction, the axon guidance molecule ephrin-A5 (17)(18)(19), and have shown that the loss...

No abstract