Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of <100mSv and dose rates of <10mGy per year; paediatric patients studies have reported increased leukaemia and brain tumours risks after doses of 30-60mGy from computed tomography scans. Questions arise, however, about the impact of even lower doses and dose rates where classical epidemiological studies have limited power but where subsets within the large cohorts are expected to have an increased risk. Further progress requires integration of biomarkers or bioassays of individual exposure, effects and susceptibility to IR. The European DoReMi (Low Dose Research towards Multidisciplinary Integration) consortium previously reviewed biomarkers for potential use in IR epidemiological studies. Given the increased mechanistic understanding of responses to low dose radiation the current review provides an update covering technical advances and recent studies. A key issue identified is deciding which biomarkers to progress. A roadmap is provided for biomarker development from discovery to implementation and used to summarise the current status of proposed biomarkers for epidemiological studies. Most potential biomarkers remain at the discovery stage and for some there is sufficient evidence that further development is not warranted. One biomarker identified in the final stages of development and as a priority for further research is radiation specific mRNA transcript profiles.

This article reviews the current knowledge on the mechanisms of adaptive response to low doses of ionizing radiation or chemical exposure. A better knowledge of these mechanisms is needed to improve our understanding of health risks at low level s of environmental or occupational exposure and their involvement in cancer or non-cancer diseases. This response is orchestrated through a multifaceted cellular program involving the concerted action of diverse stress response pathways. These evolutionary highly conserved defense mechanisms determine the cellular response to chemical and physical aggression. They include DNA damage repair (p53, ATM, PARP pathways), antioxidant response (Nrf2 pathway), immune/inflammatory response (NK-B pathway), cell survival/death pathway (apoptosis), endoplasmic response to stress (UPR response), and other cytoprotective processes including autophagy, cell cycle regulation, and the unfolded protein response. The coordinated action of these processes induced by low-dose radiation or chemicals produces biological effects that are currently estimated with the linear non-threshold model. These effects are controversial. They are difficult to detect because of their low magnitude, the scarcity of events in humans, and the difficulty of corroborating associations over the long term. Improving our understanding of these biological consequences should help humans and their environment by enabling better risk estimates , the revision of radiation protection standards, and possible therapeutic advances .

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Uranium is naturally found in the environment, and its extensive use results in an increased risk of human exposure. Kidney cells have mainly been used as in vitro models to study effects of uranium exposure, and very little about the effects on other cell types is known. The aim of this study was to assess the impact of depleted uranium exposure at the cellular level in human kidney (HEK-293), liver (HepG2), and neuronal (IMR-32) cell lines. Cytotoxicity studies showed that these cell lines reacted in a roughly similar manner to depleted uranium exposure, responding at a cytotoxicity threshold of 300-500 μM. Uranium was localized in cells with secondary ion mass spectrometry technology. Results showed that uranium precipitates at subtoxic concentrations (>100 μM). With this approach, we were able for the first time to observe the soluble form of uranium in the cell at low concentrations (10-100 μM). Moreover, this technique allows us to localize it mainly in the nucleus. These innovative results raise the question of how uranium penetrates into cells and open new perspectives for studying the mechanisms of uranium chemical toxicity.