[en] Perfluorooctanoic acid (PFOA) is a persistent organic pollutant that accumulates in the human body, leading to major health issues. Upon oral uptake, the gastrointestinal tract is the first biological barrier against PFOA. However, the localization of PFOA and its impact on the intestinal wall are largely unknown. Here we achieve a breakthrough in the knowledge of intestinal absorption, intracellular fate and toxicity of PFOA using in vitro assays combined with novel analytical imaging techniques. For the first time, we localized PFOA in the cytosol of Caco-2 cells after acute exposure using high spatial resolution mass spectrometry imaging, and we estimated the PFOA cytosolic concentration. Knowing that PFOA enters and accumulates in the intestinal cells, we also performed common toxicity assays assessing cell metabolic activity, membrane integrity, oxidative stress response, and cell respiration. This study integrating powerful analytical techniques with widely used toxicology assays provides insightful information to better understand potential negative impacts of PFOA and opens new opportunities in toxicology and life science in general.
Cambier, Sébastien; Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
Subirana, Maria A; CNRS, Université de Pau et des Pays de l'Adour, E2S UPPA, Institut des Sciences Analytiques et de Physico-Chimie pour l'Environnement et les Matériaux (IPREM), UMR 5254 Pau, France
Schaumlöffel, Dirk; CNRS, Université de Pau et des Pays de l'Adour, E2S UPPA, Institut des Sciences Analytiques et de Physico-Chimie pour l'Environnement et les Matériaux (IPREM), UMR 5254 Pau, France
Gomez, Gemma; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Pittois, Denis; Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
Guignard, Cédric; Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
SCHWAMBORN, Jens Christian ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Developmental and Cellular Biology
WIRTZ, Tom ; University of Luxembourg ; Materials Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
GUTLEB, Arno Christian ; University of Luxembourg ; Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
Mercier-Bonin, Muriel; Toxalim, Université de Toulouse, INRAE, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, Toulouse, France
AUDINOT, Jean-Nicolas ; University of Luxembourg ; Materials Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology, Belvaux, Luxembourg
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
When subcellular chemical imaging enlightens our understanding on intestinal absorption, intracellular fate and toxicity of PFOA in vitro.
Li, J., Wang, L., Zhang, X., Liu, P., Deji, Z., Xing, Y., Zhou, Y., Lin, X., Huang, Z., Per- and polyfluoroalkyl substances exposure and its influence on the intestinal barrier: an overview on the advances. Sci Total Environ, 852, 2022, 158362, 10.1016/j.scitotenv.2022.158362.
Lupton, S.J., Huwe, J.K., Smith, D.J., Dearfield, K.L., Johnston, J.J., Absorption and excretion of 14C-perfluorooctanoic acid (PFOA) in Angus cattle (Bos taurus). J Agric Food Chem 60 (2012), 1128–1134, 10.1016/j.scitotenv.2024.174071.
Pérez, F., Nadal, M., Navarro-Ortega, A., Fàbrega, F., Domingo, J.L., Barceló, D., Farré, M., Accumulation of perfluoroalkyl substances in human tissues. Environ Int 59 (2013), 354–362, 10.1016/J.ENVINT.2013.06.004.
Shi, L., Zheng, J., Yan, S., Li, Y., Wang, Y., Liu, X., Xiao, C., Exposure to perfluorooctanoic acid induces cognitive deficits via altering gut microbiota composition, impairing intestinal barrier integrity, and causing inflammation in gut and brain. J Agric Food Chem 68 (2020), 13916–13928, 10.1021/acs.jafc.0c05834.
Wang, Y., Chang, W., Wang, L., Zhang, Y., Zhang, Y., Wang, M., Wang, Y., Li, P., A review of sources, multimedia distribution and health risks of novel fluorinated alternatives. Ecotoxicol Environ Saf, 182, 2019, 109402, 10.1016/J.ECOENV.2019.109402.
Steenland, K., Zhao, L., Winquist, A., Parks, C., Ulcerative colitis and perfluorooctanoic acid (PFOA) in a highly exposed population of community residents and workers in the Mid-Ohio Valley. Environ Health Perspect, 121, 2013, 900, 10.1289/EHP.1206449.
Rashid, F., Ahmad, S., Irudayaraj, J.M.K., Effect of perfluorooctanoic acid on the epigenetic and tight junction genes of the mouse intestine. 2020, Vol. 8, Page 64 Toxics, 8, 2020, 64, 10.3390/TOXICS8030064.
Kleszczyński, K., Gardzielewski, P., Mulkiewicz, E., Stepnowski, P., Składanowski, A.C., Analysis of structure-cytotoxicity in vitro relationship (SAR) for perfluorinated carboxylic acids. Toxicol Vitr 21 (2007), 1206–1211, 10.1016/J.TIV.2007.04.020.
Kleszczyński, K., Składanowski, A.C., Mechanism of cytotoxic action of perfluorinated acids. III. Disturbance in Ca2+ homeostasis. Toxicol Appl Pharm 251 (2011), 163–168, 10.1016/J.TAAP.2011.01.002.
Miao, C., Ma, J., Zhang, Y., Chu, Y., Li, J., Kuai, R., Wang, S., Peng, H., Perfluorooctanoic acid enhances colorectal cancer DLD-1 cells invasiveness through activating NF-κB mediated matrix metalloproteinase-2/-9 expression. Int J Clin Exp Pathol, 8, 2015, 10512.
Kimura, O., Fujii, Y., Haraguchi, K., Kato, Y., Ohta, C., Koga, N., Endo, T., Uptake of perfluorooctanoic acid by Caco-2 cells: involvement of organic anion transporting polypeptides. Toxicol Lett 277 (2017), 18–23, 10.1016/j.toxlet.2017.05.012.
Han, X., Kemper, R.A., Jepson, G.W., Subcellular distribution and protein binding of perfluorooctanoic acid in rat liver and kidney. Drug Chem Toxicol 28 (2005), 197–209, 10.1081/DCT-52547.
K. Li, J. Liu, C.R.M. Grovenor, K.L. Moore, NanoSIMS Imaging and Analysis in Materials Science, Https://Doi.Org/10.1146/Annurev-Anchem-092019–032524 13 (2020) 273–292. https://doi.org/10.1146/ANNUREV-ANCHEM-092019–032524.
Nuñez, J., Renslow, R., Cliff, J.B., Anderton, C.R., NanoSIMS for biological applications: current practices and analyses. Biointerphases 13 (2018), 3–301, 10.1116/1.4993628.
De Castro, O., Audinot, J.N., Hoang, H.Q., Coulbary, C., Bouton, O., Barrahma, R., Ost, A., Stoffels, C., Jiao, C., Dutka, M., Geryk, M., Wirtz, T., Magnetic sector secondary ion mass spectrometry on FIB-SEM instruments for nanoscale chemical imaging. Anal Chem 94 (2022), 10754–10763, 10.1021/acs.analchem.2c01410.
Audinot, J.N., Philipp, P., De Castro, O., Biesemeier, A., Hoang, Q.H., Wirtz, T., Highest resolution chemical imaging based on secondary ion mass spectrometry performed on the helium ion microscope. Rep Prog Phys, 84, 2021, 10.1088/1361-6633/AC1E32.
Hilgers, A.R., Conradi, R.A., Burton, P.S., Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. Pharm Res 7, 1990, 902–910, 10.1023/A:1015937605100.
Dykstra, M.J., Reuss, L.E., Biological Electron Microscopy: Theory, Techniques, and Troubleshooting. 2003, Springer, US.
Ghasemi, M., Turnbull, T., Sebastian, S., Kempson, I., The mtt assay: utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis. Int J Mol Sci, 22, 2021, 10.3390/ijms222312827.
Quent, V.M.C., Loessner, D., Friis, T., Reichert, J.C., Hutmacher, D.W., Discrepancies between metabolic activity and DNA content as tool to assess cell proliferation in cancer research. J Cell Mol Med 14 (2010), 1003–1013, 10.1111/J.1582-4934.2010.01013.X.
Lavogina, D., Lust, H., Tahk, M.J., Laasfeld, T., Vellama, H., Nasirova, N., Vardja, M., Eskla, K.L., Salumets, A., Rinken, A., Jaal, J., Revisiting the resazurin‐based sensing of cellular viability: widening the application horizon. Biosensors, 12, 2022, 10.3390/bios12040196.
ECHA, Support Document for Identification of Pentadecafluorooctanoic Acid (PFOA) as a substance of very high concern because of its CMR and PBT properties., (2013) 1–66.
Luby-Phelps, K., Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. Int Rev Cytol 192 (2000), 189–221, 10.1016/S0074-7696(08)60527-6.
Maso, L., Trande, M., Liberi, S., Moro, G., Daems, E., Linciano, S., Sobott, F., Covaceuszach, S., Cassetta, A., Fasolato, S., Moretto, L.M., De Wael, K., Cendron, L., Angelini, A., Unveiling the binding mode of perfluorooctanoic acid to human serum albumin. Protein Sci, 30, 2021, 830, 10.1002/PRO.4036.
Stoffels, C.B.A., Angerer, T.B., Robert, H., Poupin, N., Lakhal, L., Frache, G., Mercier-Bonin, M., Audinot, J.N., Lipidomic profiling of PFOA-exposed mouse liver by multi-modal mass spectrometry analysis. Anal Chem 95 (2023), 6568–6576, 10.1021/acs.analchem.2c05470.
Florentin, A., Deblonde, T., Diguio, N., Hautemaniere, A., Hartemann, P., Impacts of two perfluorinated compounds (PFOS and PFOA) on human hepatoma cells: cytotoxicity but no genotoxicity?. Int J Hyg Environ Health 214 (2011), 493–499, 10.1016/J.IJHEH.2011.05.010.
Obiako, P., Sevcik, A., Sayes, C.M., Rapid enzymatic activity model (REAM) to decipher the toxic action of per- and polyfluoroalkyl substances. Food Chem Toxicol, 182, 2023, 114117, 10.1016/J.FCT.2023.114117.
Rampersad, S.N., Multiple applications of Alamar Blue as an indicator of metabolic function and cellular health in cell viability bioassays. Sens (Basel) 12 (2012), 12347–12360, 10.3390/S120912347.
Marchetti, P., Fovez, Q., Germain, N., Khamari, R., Kluza, J., Mitochondrial spare respiratory capacity: mechanisms, regulation, and significance in non-transformed and cancer cells. FASEB J 34 (2020), 13106–13124, 10.1096/FJ.202000767R.
Sun, T., Ji, C., Li, F., Wu, H., Time is ripe for targeting per- and polyfluoroalkyl substances-induced hormesis: global aquatic hotspots and implications for ecological risk assessment. Environ Sci Technol 58 (2024), 9314–9327, 10.1021/acs.est.4c00686.
Lin, N., Zhang, Y., Su, S., Feng, Y., Wang, B., Li, Z., Exposure characteristics of legacy and novel per- and polyfluoroalkyl substances in blood and association with hypertension among low-exposure population. J Hazard Mater, 459, 2023, 132185, 10.1016/J.JHAZMAT.2023.132185.
Tan, Y., Zeng, Z., Liang, H., Weng, X., Yao, H., Fu, Y., Li, Y., Chen, J., Wei, X., Jing, C., Association between perfluoroalkyl and polyfluoroalkyl substances and women's infertility, NHANES 2013–2016. Int J Environ Res Public Health, 19, 2022, 10.3390/ijerph192215348.
D. Fox, H. Zhang, Helium ion microscopy, 2018. https://doi.org/10.1007/978–981-13–0454-5_8.
