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A review was undertaken of studies reporting increased DNA damage in circulating blood cells and increased organ doses, for X-ray exposures enhanced by iodinated contrast media (ICM), compared to unenhanced imaging. This effect may be due to ICM molecules acting as a source of secondary radiation (Auger/photoelectrons, fluorescence X-rays) following absorption of primary X-ray photons. It is unclear if the reported increase in DNA damage to blood cells necessarily implies an increased risk of developing cancer. Upon ICM-enhancement, the attenuation properties of blood differ substantially from surrounding tissues. Increased energy deposition is likely to occur within very close proximity to ICM molecules (within a few tens of micrometres). Consequently, in many situations, damage and dose enhancement may be restricted to the blood and vessel wall only. Increased cancer risks may be possible, in cases where ICM molecules are given sufficient time to reach the capillary network and interstitial fluid at the time of exposure. In all situations, the extrapolation of blood cell damage to other tissues requires caution where contrast media are involved. Future research is needed to determine the impact of ICM on dose to cells outside the blood itself and vessel walls, and to determine the concentration of ICM in blood vessels and interstitial fluid at the time of exposure.

Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society., (© 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.)

An outline is presented of an electronically accessible database that compares the locations of mouse genes involved in DNA repair, apoptosis, cell cycle and signal transduction with those of known cancer risk modifier genes. The database has a primary but not exclusive focus on modifiers of ionizing radiation (IR) cancer risk and genes involved in IR-induced DNA damage responses. The database () provides a useful tool for assessing the role of DNA damage response genes in cancer predisposition.

Purpose: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to a single dose of X-ray or chronically exposed to low dose rate γ radiation. Materials and methods: Genomic DNA obtained from the blood or the thymus of wild type or Ogg1-deficient mice exposed to low (0.1) or intermediate/high (0.2-1 Gy) doses of radiation either by acute X-rays exposure or protracted exposure to low dose-rate c-radiation was used to analyse by PCR the presence of illegitimate TR gene rearrangements. Results: Radiation exposure does not increase the onset of TR gene trans-rearrangements in irradiated mice. In mice where it happens, trans-rearrangements remain sporadic events in developing T lymphocytes. Conclusion: We concluded that low dose/low dose rate ionizing radiation (IR) exposure does not lead to widespread inactivation of ATM-dependent mechanisms, and therefore that the mechanisms enforcing genetic stability are not impaired by IR in developing lymphocytes and lymphocyte progenitors, including BM-derived hematopoietic stem cells, in low dose/low dose rate exposed mice. [ABSTRACT FROM AUTHOR]

Purpose: Modifications of gene expression following ionizing radiation (IR) exposure of cells in vitro and in vivo are well documented. However, little is known about the dose-responses of transcriptionally responsive genes, especially at low doses. In this study, we investigated these dose-responses and assessed inter-individual variability. Materials and methods: High dose (0.5-4 Gy) and low dose (5-100 mGy) gene expression responses at 2 h and 24 h using 13 biomarkers transcriptionally regulated through the DNA damage response by the tumor suppressor p53 were investigated. Inter-individual variation was also examined. Results: High dose-response curves were best constructed using a polynomial fit while the low dose-response curves used a linear fit with linear R2 values of 0.841-0.985. Individual variation was evident in the high and low dose ranges. The FDXR, DDB2 high dose gene combination produced a mean dose estimate of 0.7 Gy for 1 Gy irradiated 'unknown' samples (95% CIs of 0.3-1.1 Gy) and 1.4 Gy for 2 Gy exposure (95% CIs of 0.6-2.1 Gy). The FDXR, DDB2, CCNG1 low dose gene combination estimated 98 mGy (95% CIs of 27-169 mGy) for 100 mGy exposure. Conclusions: These findings identify genes that fulfill some of the requirements of a good exposure biomarker even at low doses, such as sensitivity, reproducibility and simple proportionality with dose. [ABSTRACT FROM AUTHOR]

Purpose: The target cells for radiation carcinogenesis are widely held to be stem or stem-like cells. Classically, stem cells are considered to be those capable of renewing tissues while differentiated cells lose the potential to replicate. More recently it has become apparent that greater developmental plasticity exists and that cells can be reprogrammed to form induced pluripotent stem cells. Modelling of radiation cancer-risk requires understanding of the characteristics, numbers and responses of target stem cells to radiation. Therefore progress in understanding mechanisms of radiation-induced carcinogenesis is dependent on knowledge of stem cell radiobiology. Results: In this context, the European Community's network of excellence on low dose radiation risk called, 'Low Dose Research towards Multidisciplinary Integration (DoReMi)' () and the United Kingdom's Health Protection Agency organised a workshop on Stem Cells and DNA damage in Oxfordshire on 7/8 December 2011 to address issues relating to radiation, DNA damage and stem cells. In keeping with the aim of improving understanding of low dose ionising radiation health risk, a panel of experts in stem cells and radiobiology were invited to this workshop. This summary includes all presentations at this workshop and is accompanied by full reports of several speakers. [ABSTRACT FROM AUTHOR]

People are more often exposed to low as opposed to high doses of ionising radiation (IR). Knowledge on the health risks associated with exposures to ionising radiation above 100 mGy is quite well established, while lower dose risks are inferred from higher level exposure information (ICRP). The health risk assessments are mainly based on epidemiological data derived from the atomic bombing of Hiroshima and Nagasaki, medical exposure studies and follow-up studies after nuclear accidents. For the estimation of long-term stochastic radiation health effects (such as cancer) and radiation protection purposes, a linear non-threshold (LNT) model is applied. However, the general validity of the LNT hypothesis for extrapolations from effects of high to low doses (<100 mGy) and low dose-rates (<6 mGy/h) has been questioned as epidemiological studies are statistically limited at low doses and unable to evaluate low dose and low dose-rate health risks (UNSCEAR). Thus, uncertainties on health risks need to be clarified with the help of mechanistic studies. The European Network of Excellence DoReMi (2010–2016) was designed to address some of the existing uncertainties and to identify research lines that are likely to be most informative for low dose risk assessment. The present review reports the results obtained from studies addressing the induction of cancer and non-cancer effects by low dose IR as well as on individual radiation sensitivity. It is shown that low dose and low dose-rate effects are the result of complex network responses including genetic, epigenetic, metabolic and immunological regulation. Evidence is provided for the existence of nonlinear biological responses in the low and medium dose range as well as effects other than the classical DNA damage. Such effects may have a bearing on the quantitative and qualitative judgements on health effects induced by low dose radiations. [ABSTRACT FROM AUTHOR]