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Open AccessArticle

Altered Gene Expression in Dioxin-Like and Non-Dioxin-Like PCB Exposed Peripheral Blood Mononuclear Cells

1
Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany
2
IZKF, RWTH Aachen University, 52074 Aachen, Germany
3
Flemish Institute for Technological Research (VITO), Health unit, 2400 Mol, Belgium
4
Centre for Environmental Sciences, Hasselt University, 3590 Diepenbeek, Belgium
5
Institute for Occupational, Social and Environmental Medicine, RWTH Aachen University, 52074 Aachen, Germany
6
Department of Dermatology, SLK Hospital Heilbronn, 74078 Heilbronn, Germany
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2019, 16(12), 2090; https://doi.org/10.3390/ijerph16122090
Received: 12 April 2019 / Revised: 7 June 2019 / Accepted: 10 June 2019 / Published: 13 June 2019
(This article belongs to the Special Issue Endocrine Disruptors Exposure on Human Health)
Polychlorinated biphenyls (PCBs) are well known carcinogenic persistent environmental pollutants and endocrine disruptors. Our aim was to identify the possible dysregulation of genes in PCB exposed peripheral blood mononuclear cells (PBMCs) in order to give more insight into the differential pathophysiological effects of PCB congeners and mixtures, with an emphasis on immunological effects and oxidative stress. The PBMCs of a healthy volunteer (male, 56 years old) were exposed to a mixture of dioxin-like (DL)-PCBs (PCB 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189, 250 µg/L resp.) or non-dioxin-like (NDL)-PCBs (PCB 28, 52, 101, 138, 153, 180, 250 µg/L resp.) or single PCB congener (no.28, 138, 153, 180, 250 µg/L resp.). After an incubation period of 24 h, a microarray gene expression screening was performed, and the results were compared to gene expression in control samples (PBMCs treated with the vehicle iso-octane). Treatment of PBMCs with the DL-PCB mixture resulted in the largest number of differentially regulated genes (181 upregulated genes >2-fold, 173 downregulated >2-fold). Treatment with the NDL-PCB mix resulted in 32 upregulated genes >2-fold and 12 downregulated genes >2-fold. A gene set enrichment analysis (GSEA) on DL-PCB treated PBMCs resulted in an upregulation of 125 gene sets and a downregulation of 76 gene sets. Predominantly downregulated gene sets were involved in immunological pathways (such as response to virus, innate immune response, defense response). An upregulation of pathways related to oxidative stress could be observed for all PCB congeners except PCB-28; the latter congener dysregulated the least number of genes. Our experiment augments the information known about immunological and cellular stress responses following DL- as well as NDL-PCB exposure and provides new information on PCB 28. Further studies should be performed to evaluate how disruption of these pathways contributes to the development of autoimmune diseases and cancer. View Full-Text
Keywords: polychlorinated biphenyls; PBMC; gene regulation; PCB exposure; AHR; oxidative stress polychlorinated biphenyls; PBMC; gene regulation; PCB exposure; AHR; oxidative stress
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MDPI and ACS Style

Leijs, M.M.; Gan, L.; De Boever, P.; Esser, A.; Amann, P.M.; Ziegler, P.; Fietkau, K.; Schettgen, T.; Kraus, T.; Merk, H.F.; Baron, J.M. Altered Gene Expression in Dioxin-Like and Non-Dioxin-Like PCB Exposed Peripheral Blood Mononuclear Cells. Int. J. Environ. Res. Public Health 2019, 16, 2090. https://doi.org/10.3390/ijerph16122090

AMA Style

Leijs MM, Gan L, De Boever P, Esser A, Amann PM, Ziegler P, Fietkau K, Schettgen T, Kraus T, Merk HF, Baron JM. Altered Gene Expression in Dioxin-Like and Non-Dioxin-Like PCB Exposed Peripheral Blood Mononuclear Cells. International Journal of Environmental Research and Public Health. 2019; 16(12):2090. https://doi.org/10.3390/ijerph16122090

Chicago/Turabian Style

Leijs, Marike M.; Gan, Lin; De Boever, Patrick; Esser, André; Amann, Philipp M.; Ziegler, Patrick; Fietkau, Katharina; Schettgen, Thomas; Kraus, Thomas; Merk, Hans F.; Baron, Jens M. 2019. "Altered Gene Expression in Dioxin-Like and Non-Dioxin-Like PCB Exposed Peripheral Blood Mononuclear Cells" Int. J. Environ. Res. Public Health 16, no. 12: 2090. https://doi.org/10.3390/ijerph16122090

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