Transcriptomic profile indicative of immunotoxic exposure: in vitro studies in peripheral blood mononuclear cells.

K. Hochstenbach, D.M. van Leeuwen, H. Gmuender, S.B. Stolevik, U.C. Nygaard, M. Lovik, B. Granum, E. Namork, J.H.M. van Delft, H. van Loveren

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    Abstract

    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((R)) 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 promising transcriptomic profile indicative of immunotoxic exposure.
    Original languageEnglish
    Pages (from-to)19-30
    JournalToxicological Sciences
    Volume118
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2010

    Cite this

    Hochstenbach, K., van Leeuwen, D. M., Gmuender, H., Stolevik, S. B., Nygaard, U. C., Lovik, M., Granum, B., Namork, E., van Delft, J. H. M., & van Loveren, H. (2010). Transcriptomic profile indicative of immunotoxic exposure: in vitro studies in peripheral blood mononuclear cells. Toxicological Sciences, 118(1), 19-30. https://doi.org/10.1093/toxsci/kfq239