Bisphenol A (BPA) is one of the most widely utilized endocrine disruptors to which humans are exposed, particularity through ingestion. BPA is an aneugenic compound with a putative association to tumorigenesis. Although extensively studied in estrogen responsive cells, information regarding its effects on cells from the upper gastrointestinal tract exposed to free/active forms of BPA is still scarce. Similarly, BPA interactions with other drugs have been neglected, although it has been suggested to have a potential role in doxorubicin (DOX) chemoresistance. This study is intended to assess potential cytotoxic and genotoxic effects of BPA, as well as its interactions with DOX, in Human epithelial type 2 cells (Hep-2) originated from a human laryngeal carcinoma and in a DNA damage responsive cell line, the human lung fibroblasts (MRC-5). Cell viability was analyzed through the resazurin assay. The G protein-coupled estrogen receptor 1 (GPER) expression was visualized by immunodetection. Genotoxicity, namely DNA damage and oxidative DNA damage, were assessed by comet assay and micronuclei induction, and mitotic disruption was evaluated cytologically by fluorescent microscopy with DAPI staining. Cytotoxicity analysis showed that exposure to BPA per se does not affect cellular viability. Nevertheless, the genotoxic analysis showed that BPA induced an increase of DNA damage in the Hep-2 cell line and in oxidative damage in the MRC-5 cell line. An increase of micronuclei was also observed in both cell lines following BPA exposure. BPA and DOX co-exposures suggested that BPA acts as an antagonist of DOX effects in both cell lines. The interaction with DOX appears to be cell type dependent, exhibiting a non-monotonic response curve in MRC-5 cells, a GPER expressing cell line. Our study emphasizes the need for a deeper knowledge of BPA interactions, particularly with chemotherapeutic agents, in the context of risk assessment and public health.

中文翻译：

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环境相关浓度的双酚A的细胞毒性和遗传毒性作用以及与阿霉素的相互作用。

双酚A（BPA）是人类最广泛使用的内分泌干扰物之一，特别是通过摄入。BPA是一种可能与肿瘤发生有关的中毒化合物。尽管在雌激素反应性细胞中进行了广泛研究，但有关其对暴露于游离/活性形式的BPA的上消化道细胞的影响的信息仍然很少。同样，尽管已建议BPA与其他药物的相互作用在阿霉素（DOX）化学抗性中具有潜在作用，但已被忽略。这项研究旨在评估BPA在源自人喉癌的人类上皮2型细胞（Hep-2）和DNA损伤反应性细胞系中的潜在细胞毒性和遗传毒性作用，以及其与DOX的相互作用。肺成纤维细胞（MRC-5）。通过刃天青测定法分析细胞活力。G蛋白偶联雌激素受体1（GPER）的表达通过免疫检测可见。遗传毒性，即DNA损伤和氧化性DNA损伤，通过彗星试验和微核诱导进行评估，并通过DAPI染色的荧光显微镜在细胞学上评估有丝分裂破坏。细胞毒性分析表明，接触BPA本身并不影响细胞活力。然而，遗传毒性分析表明，BPA导致Hep-2细胞系DNA损伤增加，而MRC-5细胞系引起氧化损伤。BPA暴露后，在两个细胞系中也观察到微核增加。BPA和DOX共同暴露表明BPA在两种细胞系中都可作为DOX效应的拮抗剂。与DOX的相互作用似乎取决于细胞类型，在GPER表达细胞系MRC-5细胞中表现出非单调响应曲线。我们的研究强调在风险评估和公共卫生的背景下，需要更深入地了解BPA相互作用，尤其是与化学治疗剂的相互作用。