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阿弗拉托克素B诱导的伊米达环开放的瓜添加物:具有很高的致变性潜力,受到序列上下文的影响最小

Irina G Minko¹, Andrew H Kellum², Michael P Stone²

¹Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon, USA.

Environmental and molecular mutagenesis

|June 12, 2023

概括

暴露于阿弗拉托克素B1 (AFB1) 会导致肝癌. 主要的DNA损伤,AFB1-FapyGua,在所有测试的DNA序列中具有高度突变性,导致G>T突变.

科学领域:

毒理学毒理学毒理学
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

饮食中的亚弗拉托克辛B1 (AFB1) 是已知的肝细胞癌的风险因素.
AFB1的突变特征包括在特定的三核酸序列中频繁的G>T转换.
8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido) -9-hydroxyaflatoxin B1 (AFB1-FapyGua) 是关键的DNA损伤,负责AFB1诱导的突变.

研究的目的:

为了评估AFB1-FapyGuaDNA损伤的突变性潜力.
评估AFB1-FapyGua在不同DNA序列环境中的变异性,包括已知的突变热点和冷点.

主要方法:

在复制载体中引入了特定地点的AFB1-FapyGua病变.
这些载体在灵长类动物细胞中被复制.
复制产品被分离和测序以确定突变频率和类型.

主要成果:

在所有四个评估的序列环境中,AFB1-FapyGua都表现出高突变性.
G>T转换和其他基基替代发生的频率大约在80%到90%之间.
变异性在热点和冷点序列中是一致的.

结论:

AFB1-FapyGua病变是一种强大的突变原体,不管周围的DNA序列背景如何.
观察到的AFB1-FapyGua的高突变性表明,依赖序列的复制忠实性不能解释AFB1的独特突变特征.

关键词:

这是COSMIC签名SBS24的标志.基准替代替代的基础替代肝细胞癌是肝细胞癌.复制绕道的复制方法

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