Radiation cataractogenesis: A review of recent studies.

The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and it is known that cataracts can be induced by acute doses of less than 2 Gy of low-LET ionizing radiation and less than 5 Gy of protracted radiation. Although much work has been carried out in this area, the exact mechanisms of radiation cataractogenesis are still not fully understood. In particular, the question of the threshold dose for cataract development is not resolved. Cataracts have been classified as a deterministic effect of radiation exposure with a threshold of approximately 2 Gy. Here we review the combined results of recent mechanistic and human studies regarding induction of cataracts by ionizing radiation. These studies indicate that the threshold for cataract development is certainly less than was previously estimated, of the order of 0.5 Gy, or that radiation cataractogenesis may in fact be more accurately described by a linear, no-threshold model

Dose-rate effects in radiation biology and radiation protection.

Quantification of biological effects (cancer, other diseases, and cell damage) associated with exposure to ionising radiation has been a major issue for the International Commission on Radiological Protection (ICRP) since its foundation in 1928. While there is a wealth of information on the effects on human health for whole-body doses above approximately 100 mGy, the effects associated with doses below 100 mGy are still being investigated and debated intensively. The current radiological protection approach, proposed by ICRP for workers and the public, is largely based on risks obtained from high-dose and high-dose-rate studies, such as the Japanese Life Span Study on atomic bomb survivors. The risk coefficients obtained from these studies can be reduced by the dose and dose-rate effectiveness factor (DDREF) to account for the assumed lower effectiveness of low-dose and low-dose-rate exposures. The 2007 ICRP Recommendations continue to propose a value of 2 for DDREF, while other international organisations suggest either application of different values or abandonment of the factor. This paper summarises the current status of discussions, and highlights issues that are relevant to reassessing the magnitude and application of DDREF

Transcriptomic and proteomic analysis of mouse radiation-induced Acute Myeloid Leukaemia (AML).

A combined transcriptome and proteome analysis of mouse radiation-induced AMLs using two primary AMLs, cell lines from these primaries, another cell line and its in vivo passage is reported. Compared to haematopoietic progenitor and stem cells (HPSC), over 5000 transcriptome alterations were identified, 2600 present in all materials. 55 and 3 alterations were detected in the proteomes of the cell lines and primary/in vivo passage material respectively, with one common to all materials. In cell lines, approximately 50% of the transcriptome changes are related to adaptation to cell culture, and in the proteome this proportion was higher. An AML 'signature' of 17 genes/proteins commonly deregulated in primary AMLs and cell lines compared to HPSCs was identified and validated using human AML transcriptome data. This also distinguishes primary AMLs from cell lines and includes proteins such as Coronin 1, pontin/RUVBL1 and Myeloperoxidase commonly implicated in human AML. C-Myc was identified as having a key role in radiation leukaemogenesis. These data identify novel candidates relevant to mouse radiation AML pathogenesis, and confirm that pathways of leukaemogenesis in the mouse and human share substantial commonality

Keeping the ICRP recommendations fit for purpose.

The International Commission on Radiological Protection (ICRP) has embarked on a review and revision of the System of Radiological Protection that will update the 2007 General Recommendations in ICRP Publication 103. This is the beginning of a process that will take several years, involving open and transparent engagement with organisations and individuals around the world. While the System is robust and has performed well, it must adapt to address changes in science and society to remain fit for purpose. The aim of this paper is to encourage discussions on which areas of the System might gain the greatest benefit from review, and to initiate collaborative efforts. Increased clarity and consistency are high priorities. The better the System is understood, the more effectively it can be applied, resulting in improved protection and increased harmonisation. Many areas are identified for potential review including: classification of effects, with particular focus on tissue reactions; reformulation of detriment, potentially including non-cancer diseases; re-evaluation of the relationship between detriment and effective dose, and the possibility of defining detriments for males and females of different ages; individual variation in the response to radiation exposure; heritable effects; and effects and risks in non-human biota and ecosystems. Some of the basic concepts are also being considered, including the framework for bringing together protection of people and the environment, incremental improvements to the fundamental principles of justification and optimisation, a broader approach to protection of individuals, and clarification of the exposure situations introduced in 2007. In addition, ICRP is considering identifying where explicit incorporation of the ethical basis of the System would be beneficial, how to better reflect the importance of communications and stakeholder involvement, and further advice on education and training. ICRP invites responses on these and other areas relating to the review of the System of Radiological Protection

'Circulatory Disease Risk', report of the independent Advisory Group on Ionising Radiation

This AGIR report (RCE-16) reviews the epidemiological, experimental and medical evidence for radiation exposure elevating the incidence of circulatory diseases. This report is based on work conducted by the Advisory Group on Ionising Radiation (AGIR) subgroup on circulatory disease risk. Increased evidence of an association between circulatory diseases and radiation exposures has become available over recent years. Radiological protection does not currently include circulatory diseases in the calculation of health detriment from low dose exposures. It is therefore timely to review the evidence for radiation association and causation of circulatory diseases and consider the likely need and implications for radiological protection to take these diseases into account in protection of health from low dose exposures and medical exposures