Mycotoxin fumonisin B1 (FB1) is a secondary metabolite that is produced by certain Fusarium species. Although numerous studies demonstrate toxic and carcinogenic effects of FB1, the underlying mechanisms have not been fully elucidated. In this study, we evaluated the epigenetic effects of FB1 for the first time using FLO assays, which detect epigenetic changes that affect the flocculation gene (FLO1) promoter activity in budding yeast. FLO assays showed increased reporter activities of the FLO1 promoter in the presence of 10 and 20 µM FB1. FB1 (20 µM) treatments also promoted flocculation. In subsequent in vitro methylation assays of a bacterial DNA methyltransferase (DNMT), FB1 treatments increased DNMT activities. Moreover, global DNA methylation was significantly increased in HEK293 cells treated with 100 µM FB1. Taken together, these results suggest that FB1 exposure leads to unique epigenetic alterations due to increased DNMT activities and demonstrate that FB1 may be an important risk factor for epigenetic dysfunction-associated human diseases including cancer.

中文翻译：

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霉菌毒素伏马菌素 B1 对 DNA 甲基化的表观遗传作用

霉菌毒素伏马菌素 B1 (FB1) 是由某些镰刀菌产生的次级代谢物。尽管许多研究证明了 FB1 的毒性和致癌作用，但其潜在机制尚未完全阐明。在这项研究中，我们首次使用 FLO 检测评估了 FB1 的表观遗传效应，该检测检测影响出芽酵母中絮凝基因 (FLO1) 启动子活性的表观遗传变化。FLO 测定显示在 10 和 20 µM FB1 存在下 FLO1 启动子的报告活性增加。FB1 (20 µM) 处理也促进了絮凝。在随后的细菌 DNA 甲基转移酶 (DNMT) 的体外甲基化测定中，FB1 处理增加了 DNMT 活性。此外，在用 100 µM FB1 处理的 HEK293 细胞中，整体 DNA 甲基化显着增加。综合起来，