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

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2025-08-23 DOI:10.1016/j.etap.2025.104799

Francesca Coperchini , Alessia Greco , Elena Franchi , Matteo Limiroli , Laura Croce , Marsida Teliti , Benedetto Calì , Tshering Dorji , Marco Denegri , Flavia Magri , Mario Rotondi

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引用次数: 0

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 H₂DCFDA 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.

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PFCAs对原代培养球形甲状腺细胞影响的评价：对甲状腺功能相关基因、肿瘤发生和氧化应激的影响

全氟烷基羧酸盐（PFCAs）是全氟烷基和多氟烷基物质（PFAS）的一个亚群。本研究评估了C6O4、PFOA和PFHxA对人甲状腺细胞三维球体模型的影响，包括甲状腺激素功能相关基因和氧化应激标志物的变化。将正常甲状腺细胞（S-NHT）衍生的球状体暴露于PFCAs（10 ng/ml）中，以评估激素合成和作用、抗氧化酶和胚胎发生/致癌相关基因mRNA的变化。采用H2DCFDA法测定总ROS生成。我们的研究结果表明，这三种化合物都可以调节与甲状腺激素合成和作用相关的基因mRNA水平，并改变甲状腺稳态。其中，PFHxA表现出最强的甲状腺干扰作用。此外，甲状腺细胞中PAX8 mRNA表达的增加和ROS水平的升高表明PFCAs可能具有促肿瘤作用。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.