Chronic PFOA exposure in vitro causes acquisition of multiple tumor cell characteristics in rat liver cells.

Autor: Qu W; Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA. Electronic address: qu@niehs.nih.gov., Yan Y; Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Gerrish K; Molecular Genomics Core Laboratory, NIEHS, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Scappini E; Fluorescence Microscopy and Imaging Center, Signal Transduction Laboratory, NIEHS, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Tucker CJ; Fluorescence Microscopy and Imaging Center, Signal Transduction Laboratory, NIEHS, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Dixon D; Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Merrick BA; Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Jun; Vol. 89, pp. 105577. Date of Electronic Publication: 2023 Feb 26.
DOI: 10.1016/j.tiv.2023.105577
Abstrakt: Perfluorooctanoic acid (PFOA) is tumorigenic in rats and mice and potentially tumorigenic in humans. Here, we studied long-term PFOA exposure with an in vitro transformation model using the rat liver epithelial cell, TRL 1215. Cells were cultured in 10 μM (T10), 50 μM (T50) and 100 μM (T100) PFOA for 38 weeks and compared to passage-matched control cells. T100 cells showed morphological changes, loss of cell contact inhibition, formation of multinucleated giant and spindle-shaped cells. T10, T50, and T100 cells showed increased LC 50 values 20%, 29% to 35% above control with acute PFOA treatment, indicating a resistance to PFOA toxicity. PFOA-treated cells showed increases in Matrix metalloproteinase-9 secretion, cell migration, and developed more and larger colonies in soft agar. Microarray data showed Myc pathway activation at T50 and T100, associating Myc upregulation with PFOA-induced morphological transformation. Western blot confirmed that PFOA produced significant increases in c-MYC protein expression in a time- and concentration-related manner. Tumor invasion indicators MMP-2 and MMP-9, cell cycle regulator cyclin D1, and oxidative stress protein GST were all significantly overexpressed in T100 cells. Taken together, chronic in vitro PFOA exposure produced multiple cell characteristics of malignant progression and differential gene expression changes suggestive of rat liver cell transformation.
Competing Interests: Declaration of Competing Interest Authors declare that they have no conflicts of interest that might be relevant to the content of the manuscript. The authors received no external funding for this work.
(Published by Elsevier Ltd.)
Databáze: MEDLINE
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