Changes in the immuno-haematopoeitic system in rodents

Studies carried out on populations exposed to the fall-out of the Chernobyl accident have found numerous modifications in the immune system such as a change in the physiology of the thymus in a population of liquidators¹ (Yarilin et al., 1993), a decrease in the level of circulating immunoglobulins in children living in the contaminated areas (Titov et al., 1995) or a change in the percentages of the various subsets of circulating lymphocytes, again in children (Vykhovanets et al., 2000). A review of studies published in Russian on this subject was recently published (Yablokov, 2009), and highlights significant changes in the full blood count and an increase in the incidence of myelodisplastic diseases amongst populations living in contaminated areas. These changes in the immuno-haematopoietic system are mostly associated with caesium 137 contamination as well as external radiation received during clean-up operations, as in the liquidators.

We have therefore used the murine model of chronic caesium 137 ingestion previously described to analyse the haematopoietic system. Monitoring of the blood cell count, measurement of blood levels of cytokines implicated in the hematopoietic regulation, phenotyping of medullary cells and determination of the frequency of haematopoietic progenitors in the spleen and bone marrow were carried out in mice from birth up to the age of 20 weeks. The monitoring of these parameters is allows to follow the homeostasis of the haematopoietic system. However, no change in these parameters was observed in the contaminated animals, regardless of age or gender (Bertho et al., 2010).

Similarly, different functional, phenotypic parameters of the immune system were assessed.. Once again, no changes in the immune system were detected in the contaminated animals. As well the use of a vaccination model as an immune system function test did not highlight any significant change in the response to two antigens, the tetanus toxin (TT) and Keyhole lymphet haemocyanin (KLH). This response was measured by determining the blood concentration of IgG and IgM specific to the antigens used. This type of test, which represents an integrated response by the immune system, strongly suggests that the chronic ingestion of caesium 137 by mice, under our experimental conditions, does not have a major effect on either of these two physiological systems, namely the haematopoietic system and the immune system.

This lack of effect of caesium 137 in our murine model for chronic ingestion is in contradiction with the studies of human populations living in contaminated regions, which have highlighted numerous phenotypic and functional changes in both physiological systems (Titov et al., 1995, Vykhovanets et al., 2000, Yablokov, 2009, Yarilin et al., 1993). However, the health status of the population prior to the Chernobyl accident is unknown which may induce some bias in theses results. However, although our murine model is representative of the chronic ingestion observed in contaminated areas (as shown in the biokinetic studies), other factors were not taken into account in our studies. In fact, this murine model presents a certain number of limitations.

The first of these limitations is the duration of contamination. It is, in fact, difficult to compare 20 weeks’ contamination in mice with contamination of several years or tens of years’ duration in man, even if age comparisons can be made between man and rodents (Quinn, 2005). On the other hand, there is a major difference between the model described here in which the influence of a single radionuclide at a specific concentration in drinking water is determined, and populations exposed to the fall-out from the Chernobyl accident. In fact, in most studies carried out on these populations, the biological or pathological effects observed are either correlated with the average level of soil contamination due to caesium 137 in the study region (compared to a population living in an area with little or no contamination), or with estimated contamination levels a posteriori, as was the case with the liquidators. These populations are mostly exposed to low-level external irradiation and internal contamination due to the ingestion of radiocontaminated products. Moreover, in most studies, only the absorbed radiation dose due to caesium 137 is taken into account whereas other, potentially toxic radionuclides such as strontium 90 are also present in foodstuffs albeit at far lower concentrations (Cooper et al., 1992, Handl et al., 2003). The absorbed doses by these populations and calculated on the basis of environmental concentrations of caesium 137 could be then under-estimated. Based on this hypothesis, the diseases observed amongst the populations living in contaminated areas could be associated, at least in part, with risk factors other than just the ingestion of caesium 137. This model of a rodent contaminated by the chronic ingestion of caesium 137 may evolve towards a contamination model including a mixture of radionuclides with a greater range of concentrations than the single concentration used to date.

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références

(1) Liquidators : (Russian: ликвида́торы), or "clean-up workers", is the name given in the former USSR to people who were called upon to work in efforts to deal with consequences of the April 26, 1986 Chernobyl disaster on the site of the event.

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