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Tributyltin chloride (TBTC) is well known for its immunotoxic effect, in particular towards immature thymocytes. TBTC is also known to induce adipocyte differentiation in primary human bone marrow cultures, which is reflected in the decrease in a number of adipocyte-derived cytokines, chemokines and the adipocyte-linked hormone leptin. Since adipocytes influence haematopoiesis and lymphopoiesis for instance by these cytokines and hormones, we here investigated whether TBTC has an effect on specific lymphocyte subsets in human bone marrow primary cultures. FACS analysis showed a reduction of CD19/CD22-positive B cells by TBTC, both in the presence or absence of cytokines. The treatment did not cause a toxic effect on mature CD3+CD4+ and CD3+CD8+ T cells, suggesting selective TBTC toxicity on B lymphocytes in the presently used in vitro system. more...

Immunotoxicity of xenobiotics is of growing concern for various levels in society, including industry and regulatory authorities. Despite that EU legislation aims at reducing the number of laboratory animals by promoting the development of alternative validated methods. At present, immunotoxicity is generally evaluated through standard in vivo toxicity studies. The lack of alternative methods is due, in particular, to the complexity of the immune system and its responses, but possibly alternative methods for immunosuppressive chemicals are most achievable. The present study describes a long term culture (LTC) method capable of inducing the formation of lymphocyte subsets from human mononuclear bone marrow cells that may allow evaluation of lymphotoxicity. The LTC consisted of two stages: a myeloid stage to allow the formation of a stromal layer and a lymphoid stage to allow expansion of lymphocytes. Results show that the use of IL-7 in LTC inhibits precursor and mature B cells, while it supports the proliferation of CD3+CD8+ and CD3+CD4+ T-cells. The bone marrow LTC model may in future be used to test the effect of xenobiotics on stromal dependent lymphocyte formation., JRC.I.2-Validation of Alternative Methods more...

The variability of hourly values of solar wind number density, number density variation, speed, speed variation and dynamic pressure with IMF Bz and magnitude |B| has been examined for the period 1965–1986. We wish to draw attention to a strong correlation in number density and number density fluctuation with IMF Bz characterised by a symmetric increasing trend in these quantities away from Bz = 0 nT. The fluctuation level in solar wind speed is found to be relatively independent of Bz. We infer that number density and number density variability dominate in controlling solar wind dynamic pressure and dynamic pressure variability. It is also found that dynamic pressure is correlated with each component of IMF and that there is evidence of morphological differences between the variation with each component. Finally, we examine the variation of number density, speed, dynamic pressure and fluctuation level in number density and speed with IMF magnitude |B|. Again we find that number density variation dominates over solar wind speed in controlling dynamic pressure. more...

Cadmium and cadmium compounds are contaminants of the environment, food, and drinking water and are important constituents of cigarette smoke. Cd exposure has also been associated with airborne particulate CdO and with Cd-containing quantum dots in medical therapy. Adverse cadmium effects reported in the literature have stimulated during recent years an ongoing discussion to better elucidate cadmium outcomes at cell and molecular level. The present work is designed to gain an insight into the mechanism of p53 impairment at gene and protein level to understand Cd-induced resistance to apoptosis. We used a hepatoma cell line (HepG2) derived from liver, known to be metal responsive. At genotoxic cadmium concentrations no cell cycle arrest was observed. The p53 at gene and protein level was not regulated. Fluorescence images showed that p53 was correctly translocated into the nucleus but that thep21Cip1/WAF-1, a downstream protein of p53 network involved in cell cycle regulation, was not activated at the highest cadmium concentrations used. The miRNAs analysis revealed an upregulation of mir-372, an miRNA able to affectp21Cip1/WAF-1expression and promote cell cycle progression and proliferation. The role of metallothioneins and possible conformational changes of p53 are discussed. more...