Transcriptomic Profile Indicative of Immunotoxic Exposure: In Vitro Studies in Peripheral Blood Mononuclear Cells

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 European Union 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 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, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) and nonimmunotoxic chemicals (acrylamide, dimethylnitrosamine, 2-amino-3-methyl-3H-imidazo[4,5-F]quinoline, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). Using Agilent oligonucleotide microarrays, whole-genome gene expression profiles were generated, which were analyzed 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 nonimmunotoxic 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.

Immunotoxicology: challenges in the 21st century and in vitro opportunities

“…Hochstenbach et al (2010) have recently reported a set of 48 genes that can be used to distinguish immunotoxic from non-immunotoxic compounds using human peripheral blood mononuclear cells. these genes might be considered candidate biomarker genes for immunotoxicity screening.…”

Immunotoxicity, genotoxicity and epigenetic toxicity of nanomaterials: New strategies for toxicity testing?

“…To distinguish immunotoxic from non-immunotoxic compounds, human peripheral blood mononuclear cells should be preferably used. Identification of the gene signature of direct immunotoxicants should include testing the effects of large number of compounds on the transcriptome of human cells such as Jurkat T-cells (Hochstenbach et al, 2010). Diverse modes of action are involved in direct immunotoxicity and a set of pathways or genes, rather than one single gene, should be used to screen compounds for immunotoxicity and genotoxicity (Hartung and Corsini, 2013;Shao et al, 2013).…”

A foresight study on emerging technologies: State of the art of Omics technologies and potential applications in food and feed safety

“…The following studies were identified on acrylamide, including eight rat based studies (Barber and LoPachin, 2004;Barber et al, 2007;Cha et al, 2009;El-Sayyad et al, 2011;Feng et al, 2011;Hasegawa e al, 2008;Hochstenbach et al, 2010;Lampen et al, 2009;Mei et al, 2008;Oshida et al, 2011;Schwend et al, 2009;Seale et al, 2012;Sun et al, 2010;Zhang et al, 2011c;Wang Z et al, 2010). Four cell based studies involve a variety of human cell types.…”