Technical Aspects for the Evaluation of Circulating Nucleic Acids (CNAs): Circulating Tumor DNA (ctDNA) and Circulating MicroRNAs

Circulating nucleic acids (CNAs), for example, circulating tumor DNA (ctDNA) and circulating microRNA (miRNA), represent promising biomarkers in several diseases including cancer. They can be isolated from many body fluids, such as blood, saliva, and urine. Also ascites, cerebrospinal fluids, and pleural effusion may be considered as a source of CNAs, but with several and intrinsic limitations. Therefore, blood withdrawal represents one of the best sources for CNAs due to the very simple and minimally invasive way of sampling. Moreover, it can be repeated at different time points, giving the opportunity for a real-time monitoring of the disease

Biokinetic models for rats exposed to repeated inhalation of uranium: implications for the monitoring of nuclear workers

For dose assessment following chronic or accidental inhalation of radioactive aerosols, the dosimetric models of the International Commission on Radiological Protection (ICRP) provide dose coefficients, retention and excretion functions. Unknown date or dates of intake is the major source of uncertainty in dose assessment during routine monitoring of nuclear workers. The two assumptions commonly made in dose assessment from an unknown time pattern of intake have been tested experimentally with a model of repeated inhalation by rats. The hypothetical intake derived from lung measurement was relatively reliable under the two hypotheses. The hypothetical intake derived from excreta measurement depended on the choice of hypothesis and on the real time pattern of intake

The effect of repeated inhalation on the distribution of uranium in rats

For the assessment of doses after inhalation of airborne uranium compounds by workers, the International Commission on Radiological Protection (ICRP) developed compartmental models that are used to calculate reference dose coefficients and retention and excretion functions. It is assumed that each acute intake has no effect on the biokinetics of later intakes. Consequently, retention and excretion after multiple or chronic exposure are predicted using the same models as after acute exposure. This assumption was tested here on rats exposed to repeated inhalation of uranium dioxide (UO 2 ). First, excretion and organ retention were determined after a single inhalation of UO 2 . The follow-up of incorporated activity was used to design a biokinetic model for uranium inhaled by rats. Second, the biokinetics of uranium were monitored in two experiments of repeated inhalations of uranium dioxide under different intake patterns. For these two experiments, the organs' retention and excretion after repeated UO 2 inhalation were predicted using the biokinetic model and compared to the experimental measurement. Under the two sets of experimental conditions considered, the prediction of the biokinetic model based on acute exposure data was consistent with the biokinetics observed after repeated UO 2 inhalations, with the possible exception of retention in the skeleton. Copyright© Taylor & Francis Group, LLC

Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats

Depleted uranium (DU) is a radioactive heavy metal coming from the nuclear industry and used in numerous military applications. Uranium inhalation can lead to the development of fibrosis and neoplasia in the lungs. As little is known concerning the molecular processes leading to these pathological effects, some of the events in terms of genotoxicity and inflammation were investigated in rats exposed to DU by inhalation. Our results show that exposure to DU by inhalation resulted in DNA strand breaks in broncho-alveolar lavage (BAL) cells and in increase of inflammatory cytokine expression and production of hydroperoxides in lung tissue suggesting that the DNA damage was in part a consequence of the inflammatory processes and oxidative stress. The effects seemed to be linked to the doses, were independent of the solubility of uranium compounds and correlating with the type of inhalation. Repeated inhalations seemed to induce an effect of potentiation in BAL cells and also in kidney cells. Comet assay in neutral conditions revealed that DNA damage in BAL cells was composed partly by double strands breaks suggesting that radiation could contribute to DU genotoxic effects in vivo. All these in vivo results contribute to a better understanding of the pathological effect of DU inhalation. © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved

Bioaccumulation and behavioural effects of depleted uranium in rats exposed to repeated inhalations

Depleted uranium has numerous industrial and military uses. Contamination by inhalation of airborne compounds is probably the most important route of exposure. In humans, there are no data clearly demonstrating neurotoxicity of uranium, yet some experimental studies suggest a link between neurological toxicity and uranium exposure. In this work, the bioaccumulation of uranium in male rats after exposure to repeated depleted uranium dioxide inhalation (30 min inhalation at 197 mg m-3, 4 days a week for 3 weeks) has been studied, together with the behavioural effects. The uranium concentrations in the brain 1 day after the end of the exposure period varied as follows: olfactory bulb > hippocampus > frontal cortex > cerebellum, subsequently decreasing rapidly. The spontaneous locomotion activity of exposed rats was increased 1 day post exposure and the spatial working memory was less efficient 6 days post exposure, compared with control rats. These data suggest that depleted uranium is able to enter the brain after exposure to repeated inhalation, producing behavioural changes. © 2005 Elsevier Ireland Ltd. All rights reserved

Distribution and genotoxic effects after successive exposure to different uranium oxide particles inhaled by rats

In nuclear fuel cycle facilities, workers may inhale airborne uranium compounds that lead to internal contamination, with various exposure scenarios depending on the workplace. These exposures can be chronic, repeated, or acute, and can involve many different compounds. The effect of uranium after multiple scenarios of exposure is unknown. The aim of this study, therefore, was to investigate the genotoxic and biokinetics consequences of exposure to depleted insoluble uranium dioxide (UO 2 ) by repeated or acute inhalation on subsequent acute inhalation of moderately soluble uranium peroxide (UO 4 ) in rats. The results show that UO 2 repeated preexposure by inhalation increases the genotoxic effects of UO 4 inhalation, assessed by comet assay, in different cell types, when UO 4 exposure alone has no effect. At the same time, the study of UO 4 bioaccumulation showed that the UO 4 biokinetics in the kidneys, gastrointestinal tract, and excreta, but not in the lungs, were slightly modified by previous UO 2 exposures. All these results show that both genotoxic and biokinetics effects of uranium may depend on preexposure and that repeated exposure induces a potentiation effect compared with acute exposure. Copyright © Informa Healthcare

L'ICP-MS: Un outil pour le suivi des contaminations internes à l'uranium

Inductively coupled plasma mass spectrometry (ICP-MS) is considered as a very convenient technique for radionuclide measurement in the nuclear field owing to its high sensitivity and accuracy and to the possibility measuring a large range of masses. To study the different biokinetic behaviours of two different uranium oxides, insoluble UO2 and soluble UO4' in rats after successive inhalations, an analytical procedure to measure the quantity of uranium coming from each oxide was developed. The number of biological matrices studied was limited to three: two ways of the airborne uranium entry, i.e. the set lung/trachea and the gastrointestinal tract, and one way of excretion with urines. After repeated inhalations of UO2 followed by one acute inhalation of UO4' total uranium measurement in the different matrices was performed either with a kinetic phosphorescence analyzer (KPA), ICP-MS or with α- spectrometry. In addition, the amount of uranium coming from UO4' UO2 or natural uranium, respectively, was calculated by ICP-MS and α-spectrometry. All the results were compared and found to be similar. As a conclusion, the analytical procedure developed with ICP-MS was validated and ICP-MS was confirmed to be an efficient tool for the study of successive internal contaminations with uranium

L'ICP-MS: Un outil pour le suivi des contaminations internes à l'uranium

Inductively coupled plasma mass spectrometry (ICP-MS) is considered as a very convenient technique for radionuclide measurement in the nuclear field owing to its high sensitivity and accuracy and to the possibility measuring a large range of masses. To study the different biokinetic behaviours of two different uranium oxides, insoluble UO2 and soluble UO4' in rats after successive inhalations, an analytical procedure to measure the quantity of uranium coming from each oxide was developed. The number of biological matrices studied was limited to three: two ways of the airborne uranium entry, i.e. the set lung/trachea and the gastrointestinal tract, and one way of excretion with urines. After repeated inhalations of UO2 followed by one acute inhalation of UO4' total uranium measurement in the different matrices was performed either with a kinetic phosphorescence analyzer (KPA), ICP-MS or with α- spectrometry. In addition, the amount of uranium coming from UO4' UO2 or natural uranium, respectively, was calculated by ICP-MS and α-spectrometry. All the results were compared and found to be similar. As a conclusion, the analytical procedure developed with ICP-MS was validated and ICP-MS was confirmed to be an efficient tool for the study of successive internal contaminations with uranium