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大剂量双酚 A 对小鼠口腔黏膜的影响:与口腔癌的潜在关联。

Effects of high-dose bisphenol A on the mouse oral mucosa: A possible link with oral cancers.

机构信息

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Department of Chemistry, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

出版信息

Environ Pollut. 2021 Oct 1;286:117296. doi: 10.1016/j.envpol.2021.117296. Epub 2021 May 4.

DOI:10.1016/j.envpol.2021.117296
PMID:33971473
Abstract

Bisphenol A (BPA) is an endocrine disrupting chemical able to promote hormone-responsive tumors. The major route of BPA contamination being oral, the aim of the present study was to investigate BPA effects on oral cells. Here, we evaluated the impact of sub-chronic in vivo exposure to BPA and its in vitro effects on neoplastic and non-neoplastic oral cells. We evaluated the oral mucosa of mice chronically exposed to BPA (200 mg/L). The response of keratinocytes (NOK-SI) and Head and Neck (HN) Squamous Cell Carcinoma (SCC), HN12 and HN13 cell lines to BPA was examined. In vivo, BPA accumulated in oral tissues and caused an increase in epithelial proliferative activity. BPA disrupted the function of keratinocytes by altering pro-survival and proliferative pathways and the secretion of cytokines and growth factors. In tumor cells, BPA induced proliferative, invasive, pro-angiogenic, and epigenetic paths. Our data highlight the harmful effects of BPA on oral mucosa and, tumorigenic and non-tumorigenic cells. Additionally, BPA may be a modifier of oral cancer cell behavior by prompting a functional shift to a more aggressive phenotype.

摘要

双酚 A(BPA)是一种内分泌干扰化学物质,能够促进激素反应性肿瘤。BPA 的主要污染途径是口服,因此本研究旨在研究 BPA 对口腔细胞的影响。在这里,我们评估了亚慢性体内暴露于 BPA 及其对肿瘤和非肿瘤口腔细胞的体外影响。我们评估了长期暴露于 BPA(200mg/L)的小鼠的口腔黏膜。检查了角质形成细胞(NOK-SI)和头颈部(HN)鳞状细胞癌(SCC)、HN12 和 HN13 细胞系对 BPA 的反应。体内,BPA 在口腔组织中积累并导致上皮增殖活性增加。BPA 通过改变促生存和增殖途径以及细胞因子和生长因子的分泌来破坏角质形成细胞的功能。在肿瘤细胞中,BPA 诱导增殖、侵袭、促血管生成和表观遗传途径。我们的数据强调了 BPA 对口腔黏膜以及肿瘤和非肿瘤细胞的有害影响。此外,BPA 可能通过促使更具侵袭性的表型发生功能转变,从而改变口腔癌细胞的行为。

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