Effects of Heavy Metal Co-Exposure on the formation of DNA Adducts from Aristolochic Acid I: Implications for Balkan Endemic Nephropathy Development,Chemical Research in Toxicology

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Effects of Heavy Metal Co-Exposure on the formation of DNA Adducts from Aristolochic Acid I: Implications for Balkan Endemic Nephropathy Development
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2024-03-29 , DOI: 10.1021/acs.chemrestox.4c00045
Chun-Kit Au ₁ , Stefan Nagl ₁ , Wan Chan ₁

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Accumulated evidence has shown that Balkan endemic nephropathy (BEN) is a multifactorial environmental disease, with exposure to aristolochic acids (AA), and the associated DNA adduct formation, as a key causative factor of BEN development. Here, we show that coexposure to arsenic, cadmium, and iron increases the DNA adduct formation of AA in cultured kidney cells, while exhibiting both an exposure concentration and duration dependence. In contrast, coexposure to calcium and copper showed a decreasing DNA adduct formation. Because DNA damage is responsible for both the nephrotoxicity and carcinogenicity of AA, these results shed greater light on the endemic nature of BEN.

中文翻译：

重金属共同暴露对马兜铃酸 DNA 加合物形成的影响 I：对巴尔干地方性肾病发展的影响

积累的证据表明，巴尔干地方性肾病 (BEN) 是一种多因素环境疾病，接触马兜铃酸 (AA) 以及相关的 DNA 加合物形成是 BEN 发生的关键致病因素。在这里，我们发现，同时暴露于砷、镉和铁会增加培养肾细胞中 AA 的 DNA 加合物形成，同时表现出暴露浓度和持续时间依赖性。相反，同时暴露于钙和铜显示 DNA 加合物形成减少。由于 DNA 损伤是 AA 的肾毒性和致癌性的原因，这些结果进一步阐明了 BEN 的地方性本质。

更新日期：2024-03-29

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