Project description:Investigating the immunotoxic effects of exposure to chemicals usually comprises evaluation of weight and histopathology of lymphoid tissues, various lymphocyte parameters in the circulation and immune function. Immunotoxicity assessment is time consuming in humans or requires a high number of animals, making it expensive. Furthermore, reducing the use of animals in research is an important ethical and political issue. Immunotoxicogenomics represents a novel approach to investigate immunotoxicity able of overcoming these limitations. The current research, embedded in the EU project NewGeneris, aimed to retrieve gene expression profiles that are indicative of exposure to immunotoxicants. To this end, whole genome gene expression was investigated in human peripheral blood mononuclear cells (PBMC) in response to in vitro exposure to a range of immunotoxic chemicals (4-hydroxy-2-nonenal, aflatoxin B1, benzo[a]pyrene, deoxynivalenol, ethanol, malondialdehyde, polychlorinated biphenyl 153, 2,3,7,8-tetrachlorodibenzo-p-dioxin) and non-immunotoxic chemicals (acrylamide, dimethylnitrosamine, 2-amino-3-methyl-3H-imidazo[4,5-F]quinoline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). Using Agilent oligonucleotide microarrays, whole genome gene expression profiles were generated, which were analysed using Genedata’s Expressionist® software. Using Recursive Feature Elimination and Support Vector Machine, a set of 48 genes was identified that distinguishes the immunotoxic from the non-immunotoxic compounds. Analysis for enrichment of biological processes showed the gene set to be highly biologically and immunologically relevant. We conclude that we have identified a transcriptomic profile indicative of immunotoxic exposure. Keywords: Genome wide gene expression analysis, Transcriptomic profile indicative of immunotoxic exposure
Project description:Transcriptomic fingerprints in human peripheral blood mononuclear cells indicative of genotoxic and non-genotoxic carcinogenic exposure
Project description:hole Genome Expression Profile of Human Peripheral Blood Mononuclear cells Exposed to Bacillus anthracis in vitro. Peripheral blood mononuclear cells exposed to a 1 MOI (multiplicity of infection pathogenic) of the B. anhracis spores. Human Peripheral Blood Mononuclear cells Exposed to Bacillus anthracis in vitro
Project description:hole Genome Expression Profile of Human Peripheral Blood Mononuclear cells Exposed to Bacillus anthracis in vitro. Peripheral blood mononuclear cells exposed to a 1 MOI (multiplicity of infection pathogenic) of the B. anhracis spores.
Project description:For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effects markers provide limited mechanistic insight, and are unable to detect exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure. Whole genome gene expression changes were investigated in human blood cells following ex vivo exposure to a range of genotoxic and non-genotoxic carcinogenic compounds using whole genome microarrays. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic genes sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomakers of genotoxic exposure, and possibly even more importantly biomarkers of exposure to non-genotoxic carcinogens since presently no biomarkers are available. Keywords: Genome wide gene expression analysis, Transcriptomic profile indicative of immunotoxic exposure
Project description:Up to date the studies examining the gene expression profiles in response to exposure to nickel compounds have only been conducted using in vitro tissue culture systems. Here, we have compared the gene expression profiles in peripheral blood mononuclear cells (PMCs) of eight nickel refinery workers in Jinchang, China to the expression profiles of referent subjects with only environmental exposure.
Project description:For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effects markers provide limited mechanistic insight, and are unable to detect exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure. Whole genome gene expression changes were investigated in human blood cells following ex vivo exposure to a range of genotoxic and non-genotoxic carcinogenic compounds using whole genome microarrays. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic genes sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomakers of genotoxic exposure, and possibly even more importantly biomarkers of exposure to non-genotoxic carcinogens since presently no biomarkers are available. Keywords: Genome wide gene expression analysis, Transcriptomic profile indicative of immunotoxic exposure For analysis of whole genome gene expression by microarray, PBMC from five independent donors per compound were exposed for 20 hours to three concentrations, i.e. the 100% and two serial ten-fold dilutions (10% and 1%), and a DMSO or PBS vehicle control. Exposed samples were always labelled with Cy5, whereas the vehicle control samples were labelled with Cy3, and were competetively hybridized on 4x44K Agilent microarrays.
Project description:The goal of these studies is to identify genes that are regulated by glucocorticoids in human peripheral blood mononuclear cells in vitro.
Project description:The goal of these studies is to identify genes that are regulated by glucocorticoids in human peripheral blood mononuclear cells in vitro.
Project description:Study goal is to disclose features of gene expression profile of peripheral blood mononuclear cells obtained from type C cirrhotic patients with or without hepatocellular carcinomas. Keywords: gene expression profile, peripheral blood mononuclear cells, type C liver cirrhosis