环境致癌物往往会加剧内源性突变性过程,以增强瘤促进
Miaofei Xu1, Jianying Li2, Yun-Chung Hsiao3
1Division of Translational Toxicology, NIEHS, Research Triangle Park, NC, USA.
Cell reports
|July 10, 2025
概括
环境暴露,如消毒副产品,可以增加小鼠的癌症突变. 许多致癌物增强现有的突变过程,而不是创造新的,影响癌症风险评估.
科学领域:
- 环境致癌的产生
- 癌症基因组学 癌症基因组学
- 毒理学 毒理学 毒理学
背景情况:
- 环境暴露与癌症风险有关,但其特定的突变效应尚未完全理解.
- 研究由致癌物引起的瘤的突变格局对于了解癌症发展至关重要.
研究的目的:
- 确定各种环境暴露对小鼠模型中肝细胞癌 (HCC) 发展的突变影响.
- 识别与特定致癌物相关的独特突变特征,并将其与自发瘤进行比较.
主要方法:
- 来自B6C3F1/N小鼠的HCCs的整体外体序列测序.
- 对自发发生的瘤和长期暴露于十种潜在的人类致癌物质后的分析.
- 鉴定和比较突变负担,特征和动机.
主要成果:
- 暴露于化酸 (BCA) 和化酸 (BDCA) 导致突变负荷和突变特征的剂量依赖性增加 (BCA-mSBS12,BDCA-mSBS25).
- 特定的突变动机 (aTn→aCn) 富含来自BCA和BDCA暴露的HCC.
- 其他暴露和自发瘤显示了类似的突变概况,富含nCg→nTg动机.
结论:
- 许多环境致癌物可能通过放大内源性突变性过程来促进癌症,而不是通过启动独特的突变事件.
- 动物模型对于研究环境致癌和评估人类癌症风险非常有价值.
- 研究结果提供了关于环境致癌物的机制及其对癌症发展的贡献的见解.
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