基氨酸的结构-活性关系支持两种独立但相互作用的协同效应模型,用于PAC混合物的强度
John P Incardona1, Tiffany L Linbo1, James R Cameron2
1Environmental and Fisheries Science Division, Northwest Fisheries Science Center, National Marine Fisheries Service, NOAA Fisheries, Seattle, WA, USA.
原油中的多环芳香化合物 (PAC) 通过多种机制影响心脏功能,导致鱼类的发育毒性. 基化氨酸表现出协同作用,解释了原油的作用.
科学领域:
- 环境毒理学环境毒理学
- 发展生物学 发展生物学
- 海洋生物学 海洋生物学
背景情况:
- 具有三环的多环芳香化合物 (PAC),特别是 (P0) 和其基化形式,是原油对鱼类发育中毒性的关键驱动因素.
- 氨酸 (P0) 主要通过阻断离子电流影响胚胎心脏功能,而化氨酸如1-甲基-7-异烯-氨酸 (1-M,7-IP) 激活氨酸碳化合物受体 (AHR).
研究的目的:
- 调查14种基氨酸对鱼类胚胎发育的心脏毒性作用,特别是斑马鱼和大西洋鱼.
- 提出一个新的框架来了解鱼类中石化PAC混合物的发育毒性,考虑多机制途径和协同相互作用.
主要方法:
- 对鱼类胚胎进行了急性和潜发育性心脏毒性测定,这些胚胎暴露在14种不同的基中.
- 分析了对心脏发育和功能的影响,包括面缺陷.
- 测量了胚胎组织度,细胞染色体P4501AmRNA诱导,并开发了一种毒动力学模型.
主要成果:
- 所有测试的基氨酸都表现出心脏毒性,影响心脏发育和功能的特定方面.
- 面缺陷与发育性心脏毒性直接相关.
- 一个两部分毒动力学模型通过协同效应解释了PAC混合物的高强度.
结论:
- 这项研究表明,多机制性途径和氨酸之间的协同相互作用足以解释原油的高胚胎毒性作用.
- 提出了一个新的框架,用于评估鱼类中复杂的PAC混合物的发育毒性.
- 了解这些协同效应对于评估原油对水生生态系统的风险至关重要.
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