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结构上相似的真菌毒素Aflatoxin B和Sterigmatocystin在哺乳动物细胞中触发不同的和独特的高分辨率突变光谱

Pennapa Thongararm^1,2, Marisa Chancharoen^2,3, Nutchapong Suwanwong⁴

¹Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210, Thailand.

|March 26, 2025

概括

阿弗拉托克素B1 (AFB1) 和硬质囊素 (ST) 是有毒的真菌毒素. AFB1和ST之间的距离结构差异导致独特的DNA突变模式,作为暴露的生物标志物非常有用.

科学领域:

毒理学毒理学毒理学
分子生物学分子生物学
遗传学遗传学是一种遗传学.

背景情况:

阿弗拉托克素B1 (AFB1) 和硬质囊素 (ST) 是具有突变性和致癌性质的真菌毒素.
这两种毒素在结构上都相似,据信会通过环氧化物形成引起DNA损伤.
它们的独特结构特征,超出反应性环氧化物部位,被假定会影响它们的突变性特征.

研究的目的:

在小鼠胚胎纤维细胞 (MEF) 中划分和比较由AFB1和ST诱导的突变光谱.
研究分子结构,特别是远端区域在确定独特突变指纹中的作用.
评估这些独特的突变模式作为真菌毒素暴露的早期发病生物标志物的潜力.

主要方法:

暴露于AFB1和ST的MEF基因组的高分辨率双重测序.
对突变类型 (GC→TA转变) 和它们的基因组分布进行比较分析.
鉴定与每个真菌毒素相关的突变热点和模式.

主要成果:

AFB1和ST都主要诱导GC→TA突变.
AFB1比ST更具有突变性,在5'-CGC-3'和5'-CGG-3'环境中表现出明显的突变热点.
ST在5'-CGG-3'中显示出较弱的热点,其他突变分布更均,类似于氧化应激模式.

结论:

AFB1和ST的远端结构元素显著影响它们的特定突变特征.
由AFB1和ST产生的独特的突变光谱可以作为早期暴露检测的潜在生物标志物.
了解这些分子机制有助于评估与毒素暴露相关的健康风险.

关键词:

生物标志物生物标志物高分辨率的突变光谱.哺乳动物细胞哺乳动物细胞突变发生的突变发生.菌类毒素 (mycotoxins) 是一种有毒的物质.

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