A transcriptomic overview of lung and liver changes one day after pulmonary exposure to graphene and graphene oxide

Sarah S Poulsen,Stefan Bengtson,Andrew Williams,Nicklas R Jacobsen,Jesper T Troelsen,Sabina Halappanavar,Ulla Vogel

doi:10.1016/j.taap.2020.115343

Abstract

Hazard evaluation of graphene-based materials (GBM) is still in its early stage and it is slowed by their large diversity in the physicochemical properties. This study explores transcriptomic differences in the lung and liver after pulmonary exposure to two GBM with similar physical properties, but different surface chemistry.Female C57BL/6 mice were exposed by a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of graphene oxide (GO) or reduced graphene oxide (rGO). Pulmonary and hepatic changes in the transcriptome were profiled to identify commonly and uniquely perturbed functions and pathways by GO and rGO. These changes were then related to previously analyzed toxicity endpoints.GO exposure induced more differentially expressed genes, affected more functions, and perturbed more pathways compared to rGO, both in lung and liver tissues. The largest differences were observed for the pulmonary innate immune response and acute phase response, and for hepatic lipid homeostasis, which were strongly induced after GO exposure. These changes collective indicate a potential for atherosclerotic changes after GO, but not rGO exposure. As GO and rGO are physically similar, the higher level of hydroxyl groups on the surface of GO is likely the main reason for the observed differences. GO exposure also uniquely induced changes in the transcriptome related to fibrosis, whereas both GBM induced similar changes related to Reactive Oxygen Species production and genotoxicity.The differences in transcriptomic responses between the two GBM types can be used to understand how physicochemical properties influence biological responses and enable hazard evaluation of GBM and hazard ranking of GO and rGO, both in relation to each other and to other nanomaterials.

Highlights

Graphene-based materials (GBM) consist of a single or few layers of graphene sheets arranged in a 2-dimensional hexagonal lattice
graphene oxide (GO) and reduced graphene oxide (rGO) were chosen as they are produced at an industrial scale and as their dimensions are similar those of other GOs investigated in the literature (Park et al, 2015; Lee et al, 2017; Kim et al, 2018)
GO exposure was more potent in inducing differentially expressed genes (DEG), and affecting functions and canonical pathways compared to rGO exposure, both in lung and in liver

Summary

Introduction

Graphene-based materials (GBM) consist of a single or few layers of graphene sheets arranged in a 2-dimensional hexagonal lattice. The simplest form, pristine graphene, is slow to produce (Smith et al, 2019) and can be challenging to work with it due to its poor solubility and agglomeration in solutions (Niyogi et al, 2006; Kuilla et al, 2010) This has resulted in greater focus on alternative GBM. Due to the wide range of possible physicochemical properties of GBM, caused by the manufacturing processes and post-production modifications, GBM are versatile materials used in a wide range of ap plications from electronics to biomedicine This has resulted in increased interest in and increased production of GBM in the last decade (Zhu et al, 2018; GrandViewResearch, 2020).

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