EURADOS coordinated action on research, quality assurance and training of internal dose assessments.

EURADOS working group on 'Internal Dosimetry (WG7)' represents a frame to develop activities in the field of internal exposures as coordinated actions on quality assurance (QA), research and training. The main tasks to carry out are the update of the IDEAS Guidelines as a reference document for the internal dosimetry community, the implementation and QA of new ICRP biokinetic models, the assessment of uncertainties related to internal dosimetry models and their application, the development of physiology-based models for biokinetics of radionuclides, stable isotope studies, biokinetic modelling of diethylene triamine pentaacetic acid decorporation therapy and Monte-Carlo applications to in vivo assessment of intakes. The working group is entirely supported by EURADOS; links are established with institutions such as IAEA, US Transuranium and Uranium Registries (USA) and CEA (France) for joint collaboration actions.

The CONRAD approach to biokinetic modeling of DTPA decorporation therapy.

Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD).

Physiology-based modelling in radiation research: the biokinetics of plutonium.

For many years, the biokinetics of radioactive substances was calculated on the basis of mathematical criteria only. Biokinetic compartments in most cases did not correspond to anatomically defined distribution areas in an organism but were operational values. However, the quality of the resulting models depends on how accurately their assumptions reflect reality.

Radiation protection in inhomogeneous beta-gamma fields and modelling of hand phantoms with MCNPX.

The usage of beta-radiation sources in various nuclear medicine therapies is increasing. Consequently, enhanced radiation protection measures are required, as medical staff more frequently handle high-activity sources required for therapy. Inhomogeneous radiation fields make it difficult to determine absorbed dose reliably.

Biokinetic modelling of DTPA decorporation therapy: the CONRAD approach.

Administration of diethylene triamine pentaacetic acid (DTPA) can enhance the urinary excretion rate of plutonium (Pu) for several days, but most of this Pu decorporation occurs on the first day after treatment. The development of a biokinetic model describing the mechanisms of decorporation of actinides by administration of DTPA was initiated as a task of the coordinated network for radiation dosimetry project. The modelling process was started by using the systemic biokinetic model for Pu from Leggett et al.

Photo-chemically patterned polymer surfaces for controlled PC-12 adhesion and neurite guidance.

The in vitro assembling of cellular networks offering control over cell positions and connectivities by patterned culture substrates is a valuable tool for neuroscience research and other applications in cell biology. We developed a versatile technique based on polymer surface modification which allows the patterning of different cell lines for advanced tissue engineering, among them are Pheochromocytoma cells (PC-12). In contrast to other techniques applied for surface patterning, the presented photo patterning by deep UV irradiation is applicable to the widely used cell culture substrate material polystyrene (PS) and should be easily performed in most laboratories.

Neuronal outgrowth of PC-12 cells after combined treatment with nerve growth factor and a magnetic field: influence of the induced electric field strength.

In view of possible therapeutic applications of magnetic fields, the effect of an enhancement of neuronal outgrowth at higher figures of flux density and induced field strength was investigated. On the average sinusoidal magnetic field treatment at 100 microTrms/50 Hz did not change nerve growth factor (NGF) induced neurite outgrowth to a statistically significant extent. These results suggest that further increasing the induced field strength by using either higher flux densities and/or more sophisticated wave forms might be necessary to cause the neuronal response of PC-12 cells, as seen in other experiments.

Quantification of NGF-dependent neuronal differentiation of PC-12 cells by means of neurofilament-L mRNA expression and neuronal outgrowth.

We demonstrate that the degree of neuronal development of PC-12 cell differentiation can be quantified by the expression of neurofilament-L (NF-L) mRNA, when an optimal concentration of NGF (50 ng/ml) is used. During the first 7 days of NGF treatment, the relative amount of NF-L mRNA was found to increase continuously and to correlate with the outgrowth of neurites in a statistically significant way. Thus, mRNA expression is, under these conditions, a suitable means for reliably monitoring the differentiation of PC-12 cells as early as after 3 days of NGF treatment.

Action of a 50 Hz magnetic field on proliferation of cells in culture.

Proliferation of SV40-3T3 mouse fibroblasts and human HL-60 promyelocytes was studied after treatment with a sinusoidal 2 mT 50 Hz magnetic field. A single exposure of 60 minutes caused quasicyclic changes in the number of SV40-3T3 cultures as function of time after treatment, which was interpreted to be due to the induction of chronobiological mechanisms by the field. Moreover, small variations in cell cycle distribution were measured during postexposure incubation for both cell lines.

Action of 50 Hz magnetic fields on cyclic AMP and intercellular communication in monolayers and spheroids of mammalian cells.

To investigate the influence of physiological parameters such as cell density and three-dimensional cell contact on the biological action of a 2 mT/50 Hz magnetic field, mouse fibroblasts were exposed as monolayers and as multicellular spheroids. Changes in cyclic AMP content of cells and alterations in gap junction-mediated intercellular communication were measured immediately after 5 min of exposure to the field. In monolayers of intermediate cell density (1 x 10(5) cells/cm2), the field treatment caused an increase in cAMP to 121% of the control level, whereas, at 3 x 10(5) cells/cm2 (near confluence), a decrease to 88% of the unexposed cells was observed.

Cyclic AMP response in cells exposed to electric fields of different frequencies and intensities.

The action on intracellular cyclic AMP (cAMP) of therapeutically used 4000-Hz electric fields was investigated and compared with 50-Hz data. Cultured mouse fibroblasts were exposed for 5 minutes to 4000-Hz sine wave internal electric fields between 3 mV/m and 30 V/m applied within culture medium. A statistically significant decrease in cellular cAMP concentration relative to unexposed cells was observed for fields higher than 10 mV/m.

Influence of surfactant components and exposure geometry on the effects of quartz and asbestos on alveolar macrophages.

Bovine (BAM) and rat (RAM) alveolar macrophages were incubated in vitro with DQ12 quartz or UICC chrysotile asbestos either alone or in the presence of dipalmitoyl lecithin (DPL). The reaction of the cells of both species to the untreated dust particles was similar qualitatively and quantitatively, with a loss of viability and release of lactate dehydrogenase and N-acetyl-beta-glucosaminidase after 20 hr of incubation. In the presence of DPL, the toxicity of quartz to BAM disappeared completely, whereas the protective influence of the phospholipid was distinctly diminished in the case of RAM.

Cytotoxic effects of quartz and chrysotile asbestos: in vitro interspecies comparison with alveolar macrophages.

Cytotoxic effects of DQ12 quartz and chrysotile asbestos on alveolar macrophages of different animal species were compared in vitro. The type of cell reaction toward the cytotoxic dusts was always the same: a loss of cell viability (trypan blue dye exclusion test) was accompanied by the release of cytoplasmic and lysosomal enzymes. The extent of cellular destruction depended upon the amount of dust applied.

Increased density of satellite cells in the absence of fibre degeneration in muscle of myotonic mice.

A mutant mouse with a hereditary myotonia, 'arrested development of righting response', ADR, was investigated with respect to mononucleated cell populations in skeletal muscle. Upon enzymatic dissociation of different muscles from mice aged between 15 and 120 days, a 3- to 5-fold higher yield of mononucleated cells per muscle fresh weight was obtained from mice with the ADR syndrome than from control mice. Clonal cell culture showed that the absolute number of cells with myogenic potential was increased and that mutant clones had shorter generation times than wild-type controls.