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在抗癌,适应污染的鱼中,CYP1A基因中的表观遗传记忆
Samantha Carrothers1, Rafael Trevisan2,3, Nishad Jayasundara2
1Oregon Institute of Occupational Health Sciences, Oregon Health & Science University.
bioRxiv : the preprint server for biology
|August 26, 2024
概括
野生鱼类对多环芳 (PAH) 暴露产生可逆表观遗传记忆,保护它们免受PAH诱导的癌症. 这种非遗传记忆涉及细胞染色体P450 1A (CYP1A) 基因的组素修饰.
科学领域:
- 环境毒理学环境毒理学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
背景情况:
- 人类接触多环芳 (PAH) 是日益严重的公共卫生问题,气候变化和野火加剧了这一问题.
- 野生种群的Fundulus heteroclitus已经适应慢性PAH污染,表现出改变的cytochrome P450 1A (CYP1A) 基因诱导.
- CYP1A在代谢上激活PAH,其诱导水平对于确定癌症风险至关重要.
研究的目的:
- 在 * Fundulus heteroclitus * 种群中描述PAH暴露的表观遗传记忆.
- 为了研究质子修饰在跨代可逆适应PAH压力的作用.
- 了解PAH耐受性鱼类中CYP1A调节变化的长期后果.
主要方法:
- 对PAH敏感和耐受PAH的种群的繁殖和交叉养殖. *Fundulus heteroclitus*种群.
- 手动受精未经暴露的胚胎,然后进行受控的PAH挑战.
- 在*CYP1A*促进剂增强剂区域对基因素翻译后修饰的分析.
- 监测 *CYP1A* 基因表达和诱导性,以应对PAH暴露和净化.
主要成果:
- 与野生鱼类相比,耐受PAH的鱼类表现出的*CYP1A*诱导,这表明它们具有非遗传记忆.
- 表观遗传控制,特别是在*CYP1A*增强剂的双价性组织蛋白修饰,介导了F1胚胎中的这种可逆记忆.
- 在暴露于PAH时,激活质子修饰在敏感胚胎中比耐受胚胎中增加了更多.
- 耐受PAH的成年人表现出持续的*CYP1A*诱导暴露后,这表明关闭机制受损.
结论:
- *Fundulus heteroclitus* 具有表观遗传记忆,可以提供对PAH诱导癌症的可逆保护.
- 这种适应机制涉及*CYP1A*基因的动态基因子修饰,这对调节PAH代谢至关重要.
- 虽然提供了生命早期的保护,但在耐受性鱼类中持续的*CYP1A*激活可能会导致其他长期后果.
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