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

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

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

Single Real-Time Reverse Transcription-PCR assay for detection and quantification of genetically diverse HIV-1, SIVcpz, and SIVgor strains

Although antiretroviral treatment availability has improved, the virological monitoring of patients remains largely uneven across regions. In addition, viral quantification tests are suffering from human immunodeficiency virus type 1 (HIV-1) genetic diversity, fueled by the emergence of new recombinants and of lentiviruses from nonhuman primates. We developed a real-time reverse transcription-PCR (RT-PCR) assay that is relatively inexpensive and able to detect and quantify all circulating forms of HIV-1 and its simian immunodeficiency virus (SIV) precursors, SIVcpz and SIVgor. Primers and a probe were designed to detect all variants of the HIV-1/SIVcpz/SIVgor lineage. HIV-1 M plasma (n = 190; 1.68 to 7.78 log(10) copies/ml) representing eight subtypes, nine circulating recombinant forms, and 21 unique recombinant forms were tested. The mean PCR efficiency was 99%, with low coefficients of intra-and interassay variation (<5%) and a limit of quantification of <2.50 log(10) copies/ml, with a 200-mu l plasma volume. On the studied range, the specificity and the analytical sensitivity were 100 and 97.4%, respectively. The viral loads were highly correlated (r = 0.95, P < 0.0001) with the reference method (generic HIV assay; Biocentric) and had no systematic difference, irrespective of genotype. Furthermore, 22 HIV-1 O plasmas were screened and were better quantified compared to the gold-standard RealTime HIV-1 assay (Abbott), including four samples that were only quantified by our assay. Finally, we could quantify SIVcpzPtt and SIVcpzPts from chimpanzee plasma (n = 5) and amplify SIVcpz and SIVgor from feces. Thus, the newly developed real-time RT-PCR assay detects and quantifies strains from the HIV-1/SIVcpz/SIVgor lineage, including a wide diversity of group M strains and HIV-1 O. It can therefore be useful in geographical areas of high HIV diversity and at risk for the emergence of new HIV variants