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

Marike M. Leijs, Lin Gan, Patrick De Boever, André Esser, Philipp M. Amann, Patrick Ziegler, Katharina Fietkau, Thomas Schettgen, Thomas Kraus, Hans F. Merk and Jens M. Baron
Additional contact information
Marike M. Leijs: Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany
Lin Gan: IZKF, RWTH Aachen University, 52074 Aachen, Germany
Patrick De Boever: Flemish Institute for Technological Research (VITO), Health unit, 2400 Mol, Belgium
André Esser: Institute for Occupational, Social and Environmental Medicine, RWTH Aachen University, 52074 Aachen, Germany
Philipp M. Amann: Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany
Patrick Ziegler: Institute for Occupational, Social and Environmental Medicine, RWTH Aachen University, 52074 Aachen, Germany
Katharina Fietkau: Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany
Thomas Schettgen: Institute for Occupational, Social and Environmental Medicine, RWTH Aachen University, 52074 Aachen, Germany
Thomas Kraus: Institute for Occupational, Social and Environmental Medicine, RWTH Aachen University, 52074 Aachen, Germany
Hans F. Merk: Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany
Jens M. Baron: Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany

IJERPH, 2019, vol. 16, issue 12, 1-16

Abstract: 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.

Keywords: polychlorinated biphenyls; PBMC; gene regulation; PCB exposure; AHR; oxidative stress (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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