When subcellular chemical imaging enlightens our understanding on intestinal absorption, intracellular fate and toxicity of PFOA in vitro
Charlotte Stoffels, Sébastien Cambier, Maria Angels Subirana, Dirk Schaumlöffel, Gemma Gomez, Denis Pittois, Cédric Guignard, Jens C. Schwamborn, Tom Wirtz, Arno C. Gutleb, Muriel Mercier‐Bonin, Jean‐Nicolas Audinot
Abstract
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. ● High-resolution analytical imaging enables PFAS localization at subcellular level. ● Intracellular PFAS concentrations can be estimated by high-resolution analytical imaging. ● PFOA highly increases the metabolic activity of intestinal cells at low doses. ● PFOA mainly accumulates in the cytosol of intestinal cells.