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Evaluation of the effects of PFCAs on spheroid thyroid cells in primary culture: Effects on thyroid function-related genes, tumorigenesis and oxidative stress.

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Title: Evaluation of the effects of PFCAs on spheroid thyroid cells in primary culture: Effects on thyroid function-related genes, tumorigenesis and oxidative stress.
Authors: Coperchini, Francesca1 (AUTHOR), Greco, Alessia1 (AUTHOR), Franchi, Elena1 (AUTHOR), Limiroli, Matteo1 (AUTHOR), Croce, Laura1 (AUTHOR), Teliti, Marsida1 (AUTHOR), Calì, Benedetto2 (AUTHOR), Dorji, Tshering3 (AUTHOR), Denegri, Marco4 (AUTHOR), Magri, Flavia1,4 (AUTHOR), Rotondi, Mario1,4 (AUTHOR) mario.rotondi@icsmaugeri.it
Source: Environmental Toxicology & Pharmacology. Oct2025, Vol. 119, pN.PAG-N.PAG. 1p.
Subject Terms: *Perfluorooctanoic acid, *Carcinogenesis, Oxidative stress, Hormone synthesis, Fluoroalkyl compounds, Gene expression, Thyroid gland, Neoplastic cell transformation
Abstract: Perfluoroalkyl carboxylates (PFCAs) are a subgroup of Per- and Polyfluoroalkyl substances (PFAS). This study evaluated the effects of C6O4, PFOA and PFHxA on a 3D spheroid model of human thyroid cells in terms of changes in genes related to thyroid hormone functions and oxidative stress markers. Spheroids derived from normal thyroid cells (S-NHT) were exposed to PFCAs (10 ng/ml) to evaluate changes in mRNA of genes related to hormone synthesis and action, antioxidant enzymes and embryogenesis/carcinogenesis. Total ROS production was measured by using a H 2 DCFDA assay. Our results demonstrated that all three compounds modulated the level of the mRNA of genes associated with the synthesis and action of thyroid hormones, and they also altered thyroid homeostasis. In particular, PFHxA showed the most powerful thyroid disrupting effect. Moreover, increased mRNA expression of PAX8 and elevated ROS levels in thyroid cells suggested a potential pro-tumorigenic effect of PFCAs. [Display omitted] • PFCAs alter mRNA level of genes related to the synthesis of thyroid hormones. • PFHxA shows the stronger effect on these genes. • PFCAs modulate genes mRNA involved in thyroid carcinogenesis and oxidative stress. • PFOA increase the oxidative stress in S-NHT. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Toxicology & Pharmacology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Evaluation of the effects of PFCAs on spheroid thyroid cells in primary culture: Effects on thyroid function-related genes, tumorigenesis and oxidative stress.
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  Data: <searchLink fieldCode="AR" term="%22Coperchini%2C+Francesca%22">Coperchini, Francesca</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Greco%2C+Alessia%22">Greco, Alessia</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Franchi%2C+Elena%22">Franchi, Elena</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Limiroli%2C+Matteo%22">Limiroli, Matteo</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Croce%2C+Laura%22">Croce, Laura</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Teliti%2C+Marsida%22">Teliti, Marsida</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Calì%2C+Benedetto%22">Calì, Benedetto</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dorji%2C+Tshering%22">Dorji, Tshering</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Denegri%2C+Marco%22">Denegri, Marco</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Magri%2C+Flavia%22">Magri, Flavia</searchLink><relatesTo>1,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rotondi%2C+Mario%22">Rotondi, Mario</searchLink><relatesTo>1,4</relatesTo> (AUTHOR)<i> mario.rotondi@icsmaugeri.it</i>
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  Data: <searchLink fieldCode="JN" term="%22Environmental+Toxicology+%26+Pharmacology%22">Environmental Toxicology & Pharmacology</searchLink>. Oct2025, Vol. 119, pN.PAG-N.PAG. 1p.
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  Data: *<searchLink fieldCode="DE" term="%22Perfluorooctanoic+acid%22">Perfluorooctanoic acid</searchLink><br />*<searchLink fieldCode="DE" term="%22Carcinogenesis%22">Carcinogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidative+stress%22">Oxidative stress</searchLink><br /><searchLink fieldCode="DE" term="%22Hormone+synthesis%22">Hormone synthesis</searchLink><br /><searchLink fieldCode="DE" term="%22Fluoroalkyl+compounds%22">Fluoroalkyl compounds</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22Thyroid+gland%22">Thyroid gland</searchLink><br /><searchLink fieldCode="DE" term="%22Neoplastic+cell+transformation%22">Neoplastic cell transformation</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Perfluoroalkyl carboxylates (PFCAs) are a subgroup of Per- and Polyfluoroalkyl substances (PFAS). This study evaluated the effects of C6O4, PFOA and PFHxA on a 3D spheroid model of human thyroid cells in terms of changes in genes related to thyroid hormone functions and oxidative stress markers. Spheroids derived from normal thyroid cells (S-NHT) were exposed to PFCAs (10 ng/ml) to evaluate changes in mRNA of genes related to hormone synthesis and action, antioxidant enzymes and embryogenesis/carcinogenesis. Total ROS production was measured by using a H 2 DCFDA assay. Our results demonstrated that all three compounds modulated the level of the mRNA of genes associated with the synthesis and action of thyroid hormones, and they also altered thyroid homeostasis. In particular, PFHxA showed the most powerful thyroid disrupting effect. Moreover, increased mRNA expression of PAX8 and elevated ROS levels in thyroid cells suggested a potential pro-tumorigenic effect of PFCAs. [Display omitted] • PFCAs alter mRNA level of genes related to the synthesis of thyroid hormones. • PFHxA shows the stronger effect on these genes. • PFCAs modulate genes mRNA involved in thyroid carcinogenesis and oxidative stress. • PFOA increase the oxidative stress in S-NHT. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Environmental Toxicology & Pharmacology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.etap.2025.104799
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      – Code: eng
        Text: English
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      – SubjectFull: Perfluorooctanoic acid
        Type: general
      – SubjectFull: Carcinogenesis
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      – SubjectFull: Oxidative stress
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      – SubjectFull: Hormone synthesis
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      – SubjectFull: Fluoroalkyl compounds
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      – SubjectFull: Gene expression
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      – SubjectFull: Thyroid gland
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      – SubjectFull: Neoplastic cell transformation
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              Text: Oct2025
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              Y: 2025
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