Thyroid cancer risk associated with perfluoroalkyl carboxylate exposure: Assessment using a human dermal fibroblast–derived extracellular matrix–based thyroid cancer organoid,Journal of Hazardous Materials

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Thyroid cancer risk associated with perfluoroalkyl carboxylate exposure: Assessment using a human dermal fibroblast–derived extracellular matrix–based thyroid cancer organoid
Journal of Hazardous Materials ( IF 12.2 ) Pub Date : 2024-09-06 , DOI: 10.1016/j.jhazmat.2024.135771
Min Heui Yoo ₁ , Younhee Kim ₁ , Byoung-Seok Lee ₁

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The burgeoning incidence of thyroid cancer globally necessitates a deeper understanding of its etiological factors. Emerging research suggests a link to environmental contaminants, notably perfluoroalkyl carboxylates (PFACs). This study introduces a novel biomaterial-based approach for modeling thyroid cancer and assesses PFAC exposure–related health risks. This biomaterial-centric methodology enabled a realistic simulation of long-term, low-dose PFAC exposure, yielding critical insights into their carcinogenic potential. Initially, the no observed adverse effect level concentration of 10 μM for four different PFACs, determined using cytotoxicity tests in 2D cell cultures, was employed with thyroid cancer organoids. Specifically, these organoids were exposed to 10 μM of PFACs, refreshed every 3 days over a period of 21 days. The impact of these PFACs on the organoids was assessed using western blotting and immunofluorescence, complemented by high-content screening imaging. This evaluation focused on thyroid-specific biomarkers, epithelial–mesenchymal transition markers, and the proliferation marker Ki-67. Findings indicated significant alterations in these markers, particularly with long-chain PFACs, suggesting an increased risk of thyroid cancer progression and metastasis upon prolonged exposure. This research advances our understanding of thyroid cancer pathology within the context of environmental health risks by investigating the effects of low-dose, long-term exposure to PFACs on human thyroid cancer organoids. The findings reveal the potential carcinogenic risk associated with these substances, emphasizing the urgent need for stricter regulatory controls.

中文翻译：

与全氟烷基羧酸盐暴露相关的甲状腺癌风险：使用基于人真皮成纤维细胞来源的细胞外基质的甲状腺癌类器官进行评估

甲状腺癌的全球发病率迅速上升，需要更深入地了解其病因。新兴研究表明，这与环境污染物有关，特别是全氟烷基羧酸盐（PFAC）。本研究介绍了一种基于生物材料的新型甲状腺癌建模方法，并评估了与 PFAC 暴露相关的健康风险。这种以生物材料为中心的方法能够对长期、低剂量 PFAC 暴露进行真实模拟，从而对其潜在的致癌性产生重要见解。最初，使用在 2D 细胞培养物中进行细胞毒性测试测定的四种不同 PFAC 未观察到的 10 μM 不良反应水平浓度与甲状腺癌类器官一起使用。具体来说，这些类器官暴露于 10 μM PFAC，在 21 天内每 3 天刷新一次。使用蛋白质印迹和免疫荧光评估这些 PFAC 对类器官的影响，并辅以高内涵筛选成像。该评估侧重于甲状腺特异性生物标志物、上皮-间充质转化标志物和增殖标志物 Ki-67。研究结果表明这些标志物发生了显着变化，尤其是长链 PFAC，表明长期暴露会增加甲状腺癌进展和转移的风险。这项研究通过研究低剂量、长期暴露于 PFAC 对人类甲状腺癌类器官的影响，在环境健康风险的背景下推进了我们对甲状腺癌病理学的理解。研究结果揭示了与这些物质相关的潜在致癌风险，强调了迫切需要更严格的监管控制。

更新日期：2024-09-06

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