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. and the biokinetic model for DTPA compounds of International Commission on Radiation Protection Publication 53. The chelation of Pu and DTPA to Pu-DTPA was treated explicitly and is assumed to follow a second-order process. It was assumed that the chelation takes place in the blood and in the rapid turnover soft tissues compartments of the Pu model, and that Pu-DTPA behaves in the same way as administered DTPA. First applications of this draft model showed that the height of the peak of urinary excretion after administration of DTPA was determined by the chelation rate. However, repetitions of DTPA administration shortly after the first one showed no effect in the application of the draft model in contrast to data from real cases. The present draft model is thus not yet realistic. Therefore several questions still have to be answered, notably about where the Pu-DTPA complexes are formed, which biological ligands of Pu are dissociated, if Pu-DTPA is stable and if the biokinetics of Pu-DTPA excretion is similar to that of DTPA. Further detailed studies of human contamination cases and experimental data about Pu-DTPA kinetics will be needed in order to address these issues. The work will now be continued within a working group of EURADOS.

No abstract

No abstract

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). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.

No abstract

Background: Thus far, a well-established logical pattern of malignancy does not exist. The current approach to cancer properties is primarily descriptive with usually, for each of them, extensive analyses of the underlying associated biomolecular mechanisms. However, this remains a catalog and it would be valuable to determine the organizational chart that could account for their implementation, hierarchical links and input into tumor regulation. Hypothesis: Striking phenotypic similarities exist between trophoblast (invasive and expanding early placenta) and cancer regarding cell functions, logistics of development, means of protection and capacity to hold sway over the host organism. The concept of cancer cell trophoblastic-like transdifferentiation appears to be a rational proposal in an attempt to explain this analogy and provide a consistent insight into how cancer cells are functioning. Should this concept be validated, it could pave the way to promising research and therapeutic perspectives given that the trophoblastic properties are vital for the tumor while they are permanently epigenetically turned off in normal cells. Specifically targeting expression of the trophoblastic master genes could thereby be envisaged to jeopardize the tumor and its metastases without, in principle, inducing adverse side effects in the healthy tissues. Conclusion: A wide set of functional features of cancer tissue regulation, including some apparently paradoxical facts, was reviewed. Cancer cell misuse of physiological trophoblastic functions can clearly account for them, which identifies trophoblastic-like transdifferentiation as a likely key component of malignancy and makes it a potential relevant anticancer target.

Background: Cancer is mainly watched through the prism of random mutations and related corruption of signaling pathways. However, it would seem puzzling to explain the tumor organization, pugnacity and steady evolution of the tumorous disease and, moreover, a systematic ascendancy over the healthy tissues, only through stochastic genomic alterations.Malignancy specific properties: Considering the core characteristics of cancer cells, it appears that two major sets of properties are emerging, corresponding to wellidentified physiological phenotypes, i.e., (1) the trophoblastic logistical functions for cell survival, protection, expansion, migration, and host-tissue conditioning for angiogenesis and immune tolerance and (2) the sexual functions for genome maintenance. To explain the resurgence of these trophoblastic and sexual phenotypes, a particular cell reprogramming, to be called "malignant transdifferentiation" in view of its key role in the precancer-to-cancer shift, appears to be a convincing hypothesis.perspectives: The concept of malignant transdifferentiation, in addition to oncogenic mutations, would determine a more rational approach of oncogenesis and would open so far unexplored ways of therapeutic actions. Indeed, the trophoblastic phenotype would be a good candidate for therapeutic purposes because, on the one hand, it covers numerous properties that all are vital for the tumor, and on the other hand, it can be targeted with potentially no risk of affecting the healthy tissues as it is not expressed there after birth.

RÉSUMÉABSTRACT implication of the occupational physician and of the expert in the management and the dosimetry of an accidental contamination.This case concerns a wound contaminated by plutonium. In managing the consequences of such an incident, the occupational physician of a nuclear installation has to solve various questions in the field of dosimetry, communication and regulation. Dosimetry and risk evaluation of internal contamination are complex. Dose limits are annual limits and it is dificult to explain to the victim that for internal contamination the decision concerning the ability to work in controlled areas is determined on the basis of a commiîted dose on 50 years. Moreover, the notification of such an incident to the employer, to the labour inspectorate and to the govermental organism of control of radiation protection needs an important involvement in the domain of information. This case allows us to describe various practical aspects of medical management and dosimetry. The follow-up of measurements and therapy is given for a period of more than five years.