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PFOA, PFHxA and C6O4 differently modulate the expression of CXCL8 in normal thyroid cells and in thyroid cancer cell lines

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Abstract

Industrial chemical PFAS are persistent pollutants. Long chain PFAS were taken out of production due to their risk for human health, however, new congeners PFAS have been introduced. The in vitro effects of the long-chain PFOA, the short-chain PFHxA and the new-generation C6O4 were evaluated in normal and in thyroid cancer cell lines in terms of cell viability and proliferation, and secretion of a pro-tumorigenic chemokine (CXCL8), both at the mRNA and at the protein level. The Nthy-ory 3–1 normal-thyroid cell line, the TPC-1 and the 8505C (RET/PTC rearranged and BRAFV600e mutated, respectively) thyroid-cancer cell lines were exposed to increasing concentrations of each PFAS in a time-course. We evaluated viability using WST-1 (confirmed by AnnexinV/PI) and proliferation using the cristal-violet test. To evaluate CXCL8 mRNA we used RT-PCR and measured CXCL8 in the supernatants by ELISA. The exposure to none PFAS did not affect thyroid cells viability (except for a reduction of 8505C cells viability after 144 h) or proliferation. Individual PFAS differently modulated CXCL8 mRNA and protein level. PFOA increased CXCL8 both at mRNA and protein level in the three cell lines; PFHxA increased CXCL8 mRNA in the three cell lines, but increased the protein only in TPC-1 cells; C6O4 increased the CXCL8 mRNA only in thyroid cancer cell lines, but never increased the CXCL8 protein. The results of the present study indicate that the in vitro exposure to different PFAS may modulate both at the mRNA and secreted protein levels of CXCL8 in normal and cancer thyroid cells. Strikingly different effects emerged according to the specific cell type and to the targeted analyte (CXCL8 mRNA or protein).

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Acknowledgements

Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for proposals No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union – Next Generation EU; Award Number: Project code PE00000003, Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001, Project title “ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security – Working ON Foods”. This work was partially supported by the ‘Ricerca Corrente’ funding scheme of the Ministry of Health Italy.

Funding

This research was supported by Solvay Specialty Polymers Italy S.p.A. The commissioning partly funded the consumables used in this study. The funder had no role in planning or executing the research, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Internal Medicine and Therapeutics, University of Pavia, Pavia (PV), 27100, Italy

    Francesca Coperchini, Laura Croce, Flavia Magri & Mario Rotondi

  2. Department of Clinical and Experimental Medicine, Endocrinology Unit, University of Pisa (PI), via Paradisa 2, 56124, Pisa, Italy

    Giuseppina De Marco & Massimo Tonacchera

  3. Istituti Clinici Scientifici Maugeri IRCCS, Unit of Endocrinology and Metabolism, Laboratory for Endocrine Disruptors, Pavia (PV), 27100, Italy

    Laura Croce, Alessia Greco, Flavia Magri, Mario Rotondi & Luca Chiovato

  4. NBFC, National Biodiversity Future Center, Palermo (PA), 90133, Italy

    Laura Croce & Mario Rotondi

  5. Istituti Clinici Scientifici Maugeri IRCCS, Unit of Molecular Cardiology, 27100, Pavia (PV), Italy

    Marco Denegri

  6. Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100, Pavia (PV), Italy

    Marcello Imbriani

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  1. Francesca Coperchini
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Contributions

Francesca Coperchini: Conceptualization, Methodology, Laura Croce: Software, statystical analysis, images quality, writing; Marco Denegri, Alessia Greco, Giuseppina De Marco: real time PCR experiments, writing; Massimo Tonacchera: data analysis, editing, supervision, Flavia Magri: methodological supervision; Marcello Imbriani: reviewing; Mario Rotondi: Writing- Reviewing: Luca Chiovato: supervision editing.

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Correspondence to Luca Chiovato.

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Coperchini, F., De Marco, G., Croce, L. et al. PFOA, PFHxA and C6O4 differently modulate the expression of CXCL8 in normal thyroid cells and in thyroid cancer cell lines. Environ Sci Pollut Res 30, 63522–63534 (2023). https://doi.org/10.1007/s11356-023-26797-6

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