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Research article - Peer-reviewed, 2020

An integrated transcriptomic- and proteomic-based approach to evaluate the human skin sensitization potential of glyphosate and its commercial agrochemical formulations

Lindberg, Tim; de Avila, Renato Ivan; Zeller, Kathrin S.; Levander, Fredrik; Eriksson, Dennis; Chawade, Aakash; Lindstedt, Malin;

Abstract

We investigated the skin sensitization hazard of glyphosate, the surfactant polyethylated tallow amine (POEA) and two commercial glyphosate-containing formulations using different omics-technologies based on a human dendritic cell (DC)-like cell line. First, the GARDTskin assay, investigating changes in the expression of 200 transcripts upon cell exposure to xenobiotics, was used for skin sensitization prediction. POEA and the formulations were classified as skin sensitizers while glyphosate alone was classified as a non-sensitizer. Interestingly, the mixture of POEA together with glyphosate displayed a similar sensitizing prediction as POEA alone, indicating that glyphosate likely does not increase the sensitizing capacity when associated with POEA. Moreover, mass spectrometry analysis identified differentially regulated protein groups and predicted molecular pathways based on a proteomic approach in response to cell exposures with glyphosate, POEA and the glyphosate-containing formulations. Based on the protein expression data, predicted pathways were linked to immunologically relevant events and regulated proteins further to cholesterol biosynthesis and homeostasis as well as to autophagy, identifying novel aspects of DC responses after exposure to xenobiotics. In summary, we here present an integrative analysis involving advanced technologies to elucidate the molecular mechanisms behind DC activation in the skin sensitization process triggered by the investigated agrochemical materials. Significance: The use of glyphosate has increased worldwide, and much effort has been made to improve risk assessments and to further elucidate the mechanisms behind any potential human health hazard of this chemical and its agrochemical formulations. In this context, omics-based techniques can provide a multiparametric approach, including several biomarkers, to expand the mechanistic knowledge of xenobiotics-induced toxicity. Based on this, we performed the integration of GARDTskin and proteomic data to elucidate the skin sensitization hazard of POEA, glyphosate and its two commercial mixtures, and to investigate cellular responses more in detail on protein level. The proteomic data indicate the regulation of immune response-related pathways and proteins associated with cholesterol biosynthesis and homeostasis as well as to autophagy, identifying novel aspects of DC responses after exposure to xenobiotics. Therefore, our data show the applicability of a multiparametric integrated approach for the mechanism-based hazard evaluation of xenobiotics, eventually complementing decision making in the holistic risk assessment of chemicals regarding their allergenic potential in humans.

Keywords

Roundup; Glyphosate; POEA; Allergic contact dermatitis; Proteomics; Transcriptomics

Published in

Journal of Proteomics

2020, volume: 217, article number: 103647
Publisher: ELSEVIER

Authors' information

Lindberg, Tim
Lund Univ
de Avila, Renato Ivan
SenzaGen AB
de Avila, Renato Ivan
Univ Fed Goias
de Avila, Renato Ivan
Lund Univ
Zeller, Kathrin S.
Lund Univ
Levander, Fredrik
Lund Univ
Swedish University of Agricultural Sciences, Department of Plant Breeding
Swedish University of Agricultural Sciences, Department of Plant Breeding
Lindstedt, Malin
Lund Univ

Sustainable Development Goals

SDG3 Good health and wellbeing

UKÄ Subject classification

Immunology in the medical area
Bioinformatics and Systems Biology

Publication Identifiers

DOI: https://doi.org/10.1016/j.jprot.2020.103647

URI (permanent link to this page)

https://res.slu.se/id/publ/105612