TY - JOUR

T1 - Pro-inflammatory response and genotoxicity caused by clay and graphene nanomaterials in A549 and THP-1 cells

AU - Di Ianni, Emilio

AU - Moller, Peter

AU - Vogel, Ulla Birgitte

AU - Jacobsen, Nicklas Raun

PY - 2021

Y1 - 2021

N2 - Nanoclays and graphene oxide nanomaterials represent a class of materials sharing similar shapes constituted of high aspect ratio platelets. The increased production of these materials for various industrial applications in -creases the risk of occupational exposure, consequently with elevated risk of adverse reactions and development of pulmonary diseases, including lung cancer. In this study, pro-inflammatory responses and genotoxicity were assessed in alveolar epithelial cells (A549) and activated THP-1 macrophages (THP-1a) after exposure to three nanoclays; a pristine (Bentonite) and two surface modified (benzalkonium chloride-coated Nanofil9, and dialkyldimethyl-ammonium-coated NanofilSE3000); graphene oxide (GO) and reduced graphene oxide (r-GO) nanomaterials. The pro-inflammatory response in terms of IL-8 expression was strongest in cells exposed to Bentonite, whereas surface modification resulted in decreased toxicity in both cell lines when exposed to Nanofil9 and NanofilSE3000. GO and r-GO induced a pro-inflammatory response in A549 cells, while no effect was detected with the two nanomaterials on THP-1a cells. The pro-inflammatory response was strongly corre-lated with in vivo inflammation in mice after intra-tracheal instillation when doses were normalized against surface area. Genotoxicity was assessed as DNA strand breaks, using the alkaline comet assay. In A549 cells, an increase in DNA strand breaks was detected only in cells exposed to Bentonite, whereas Bentonite, Nano-filSE3000 and GO caused an increased level of genotoxicity in THP-1a cells. Genotoxicity in THP-1a cells was concordant with the DNA damage in bronchoalveolar lavage fluid cells following 1 and 3 days after intra-tracheal instillation in mice. In conclusion, this study shows that surface modification of pristine nanoclays re-duces the inflammatory and genotoxic response in A549 and THP-1a cells, and these in vitro models show comparable toxicity to what seen in previous mouse studies with the same materials.

AB - Nanoclays and graphene oxide nanomaterials represent a class of materials sharing similar shapes constituted of high aspect ratio platelets. The increased production of these materials for various industrial applications in -creases the risk of occupational exposure, consequently with elevated risk of adverse reactions and development of pulmonary diseases, including lung cancer. In this study, pro-inflammatory responses and genotoxicity were assessed in alveolar epithelial cells (A549) and activated THP-1 macrophages (THP-1a) after exposure to three nanoclays; a pristine (Bentonite) and two surface modified (benzalkonium chloride-coated Nanofil9, and dialkyldimethyl-ammonium-coated NanofilSE3000); graphene oxide (GO) and reduced graphene oxide (r-GO) nanomaterials. The pro-inflammatory response in terms of IL-8 expression was strongest in cells exposed to Bentonite, whereas surface modification resulted in decreased toxicity in both cell lines when exposed to Nanofil9 and NanofilSE3000. GO and r-GO induced a pro-inflammatory response in A549 cells, while no effect was detected with the two nanomaterials on THP-1a cells. The pro-inflammatory response was strongly corre-lated with in vivo inflammation in mice after intra-tracheal instillation when doses were normalized against surface area. Genotoxicity was assessed as DNA strand breaks, using the alkaline comet assay. In A549 cells, an increase in DNA strand breaks was detected only in cells exposed to Bentonite, whereas Bentonite, Nano-filSE3000 and GO caused an increased level of genotoxicity in THP-1a cells. Genotoxicity in THP-1a cells was concordant with the DNA damage in bronchoalveolar lavage fluid cells following 1 and 3 days after intra-tracheal instillation in mice. In conclusion, this study shows that surface modification of pristine nanoclays re-duces the inflammatory and genotoxic response in A549 and THP-1a cells, and these in vitro models show comparable toxicity to what seen in previous mouse studies with the same materials.

KW - Organo-modified

KW - Occupational health

KW - In vitro alternative

KW - Risk assessment

KW - Respiratory toxicology

KW - OXIDATIVE STRESS

KW - OXIDE

KW - DNA

KW - CYTOTOXICITY

KW - TOXICITY

KW - NANOPARTICLES

KW - MECHANISMS

KW - EXPOSURE

KW - SIZE

U2 - 10.1016/j.mrgentox.2021.503405

DO - 10.1016/j.mrgentox.2021.503405

M3 - Journal article

C2 - 34798932

VL - 872

JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

SN - 1383-5718

M1 - 503405

ER -