Dietary exposure to deoxynivalenol (DON) from contaminated cereal crops is frequent in Europe, and farm workers who handle grain or silage may be at additional risk. In this study we refined a urinary assay for DON and present a novel assay for the DON metabolite de-epoxy-deoxynivalenol (DOM-1). These were applied to a pilot survey of male French farmers (n = 76, aged 23-74). DON was detected in 75/76 samples (range 0.5-28.8 ng/mL) and DOM-1 in 26/76 samples (range 0.2-2.8 ng/mL). In multivariate analysis including creatinine as a covariate, bread consumption, other cereal consumption, and maize acreage contributed to the model, explaining the variation in urinary "DON and DOM-1" concentration combined (R(2) = 0.33). This is the first exposure biomarker survey for DON in a French population, and the first demonstration of urinary DOM-1 in humans. Further investigations into occupational activity, handling, or airborne exposures would be informative.

Increasing incidence of non-Hodgkin's lymphoma have been associated repeatedly with farming occupation and particular attention focused on the role of pesticide exposure to potentially explain part of this trend. A genetic hallmark of non-Hodgkin's lymphoma is the presence of recurrent chromosomal translocations involving the immunoglobulin heavy chain gene. Of these, the t(14;18), which deregulates BCL2 expression and inhibits apoptosis, is the most frequent in follicular lymphoma and has been detected consistently in peripheral blood lymphocytes of healthy individuals. As BCL2-IGH translocation represents an early step of the malignant process, we evaluated the occurrence and molecular characteristics of BCL2-IGH translocation in 56 individuals occupationally exposed to pesticides in open field farming They were selected from a representative cohort of farmers with a well-defined assessment of pesticide exposure taking into account potential confounding factors, smoking, sunlight, and age. Our results suggest that occupational exposure to pesticides would increase BCL2-IGH prevalence together with the frequency of BCL2-IGH-bearing cells especially during the high pesticide use period. Distribution of BCL2 or IGH breakpoint positions seemed to be independent of pesticide exposure and was similar to those found in other healthy populations or lymphoma patients. Finally, these results provide additional evidence that BCL2-IGH translocation measurements could be a measure of acquired genetic instability in relation to genotoxic exposure in a gene directly relevant in term of lymphomagenesis.

20 PMBLs, five cHL (L428, L1236, HDLM-2, KM-H2, and L540) and two PMBL cell lines (MedB-1 and Karpas1106) for presence of the activating V617F mutation in the JAK2 gene by sitespecific restriction analysis ( Figure 1a).Our results demonstrate the absence of the G-T mutation in both alleles of JAK2 since BsaXI completely cleaved the PCR product yielded from DNA of all cell lines, PMBLs, and cHLs ( Figure 1b).Nevertheless, there is evidence for constitutive JAK/STAT activity in PMBL and cHL. We lately found mutations in SOCS-1 (suppressor of cytokine signaling-1), a negative regulator of this pathway. In PMBL lines MedB-1 and Karpas1106, SOCS-1 defects prolonged activity of phospho-JAK2 leading to constitutive STAT5 activation. 8,9 Moreover, in neoplastic cells of cHLs SOCS-1 mutations were equally frequent and were associated with nuclear accumulation of phosph-STAT5 indicating constitutive STAT5 activity. 10Our analysis of JAK2 excluded the V617F mutation in cHL and PMBL. We conclude that this activating mechanism of JAK2 is not operative in these lymphomas. Hence, attention reconcentrates on other JAK/STAT activating mechanisms, for example, mutations or silencing of negative regulators like SOCS-1 and/or protein-tyrosine phosphatases.

Circulating miRNAs are promising biomarkers in oncology but have not yet been implemented in the clinic given the lack of concordance across studies. In order to increase the cross‐studies reliability, we attempted to reduce and to control the circulating miRNA expression variability between patients. First, to maximize profiling signals and to reduce miRNA expression variability, three isolation kits were compared and the NucleoSpin® kit provided higher miRNA concentrations than the other widely used kits. Second, to control inter‐sample variability during the profiling step, the exogenous miRNAs normalization method commonly used for RT‐qPCR validation step was adapted to microarray experiments. Importantly, exogenous miRNAs presented two‐fold lower inter‐sample variability than the widely used endogenous miR‐16‐5p reflecting that the latter is subject to both biological and technical variability. Although Caenorhabditis elegans miRNAs isolation yields were heterogeneous, they correlated to each other and to their geometrical mean across samples. The normalization based on the geometrical mean of three exogenous miRNAs increased the correlation up‐to 0.97 between the microarrays and individual RT‐qPCR steps of circulating miRNAs expression. Overall, this new strategy open new avenue to identify reliable circulating miRNA signatures for translation into clinical practice.