AI Article Synopsis
- PFOA is linked to tumor development in both rats and potentially humans; this study investigates the effects of long-term exposure to PFOA on rat liver cells over 38 weeks.* -
- Cells exposed to high concentrations of PFOA displayed significant changes, such as loss of normal cell limitations and increased resistance to toxicity, along with abnormal cell shapes.* -
- The study found that PFOA treatment activated specific pathways and increased the expression of proteins associated with cancer progression, indicating that chronic exposure may lead to malignant changes in liver cells.*
Article Abstract
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 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427995 | PMC |
| http://dx.doi.org/10.1016/j.tiv.2023.105577 | DOI Listing |
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