通过剂量依赖的酵母功能基因组学方法评估有机酸盐阻燃剂的生物活性
Miao Guan1, Xiaoyang Wang1, Xinyuan Xu1
1Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Rd., Nanjing, Jiangsu 210023, China.
Environment international
|March 24, 2024
概括
有机酸盐阻燃剂 (OPFRs) 由于复杂的毒性而带来风险. 这项研究揭示了早期的分子反应,特别是在脂质代谢中,并确定了耐药的酵母菌株,用于风险评估和开发更安全的替代品.
科学领域:
- 环境毒理学环境毒理学
- 功能性基因组学是一种功能性基因组学.
- 酵母模型系统的模型系统
背景情况:
- 有机酸盐阻燃剂 (OPFR) 是广泛存在的环境污染物,其毒性机制尚不完全理解.
- 对OPFRs的早期分子反应对于准确的风险评估至关重要,但仍然在很大程度上未被阐明.
研究的目的:
- 通过使用剂量依赖的功能基因组学方法系统地探索14个OPFRs的全基因组生物途径扰乱.
- 确定受OPFRs影响的生物途径的起点 (POD),并了解结构-活动关系.
- 为OPFR风险评估建立一个强大的平台,并指导开发更绿色的替代品.
主要方法:
- 使用的Saccharomyces cerevisiae在24小时内暴露在14种不同替代剂 (,素,) 的OPFR中.
- 采用剂量依赖的功能基因组学方法来分析全基因组基因表达并识别POD.
- 通过将化学性质 (碳素数,logKow) 与生物效能相关联,研究了结构-活性关系.
主要成果:
- 确定了14种OPFR的生物功效 (PODDRG20),范围为0.013至35.079μM,其中增酸盐 (TnBP) 的功效最高.
- 在碳素数/logKow和POD之间建立了显著的负相关性,影响脂质代谢.
- 确定了包括脂质代谢,氧化应激,DNA损伤和MAPK信号传递在内的关键扰乱路径,脂质代谢是最敏感的.
结论:
- 脂质代谢是OPFR毒性的主要分子标.
- 一种耐药的酵母突变 (ERG2淘汰) 被确定为研究OPFR中毒的有价值工具.
- 该研究为OPFR风险评估提供了一个有效的平台,并为设计更安全的阻燃剂提供了信息.
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