在14天反复口服后对1,4-二氧化的毒性进行了组织病理学和毒基因组学评估
Hiroshi Honda1, Kentaro Yamamoto2, Mutsumi Shiraishi2
1R&D Safety Science Research, Kao Corporation, 2606 Akabane, Ichikai-Machi, Haga-Gun, Tochigi 321-3497, Japan.
Environmental toxicology and pharmacology
|November 27, 2025
概括
1,4-二氧化 (DON) 在反复口服暴露后会在老鼠中引起肝脏和脏损伤. 基因表达的变化表明氧化应激和免疫反应是其非基因毒性致癌途径的关键.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 1,4-二氧化 (DON) 被广泛使用,但其肝癌致癌机制尚不清楚.
- 了解DON的毒性潜力和高剂量的肝脏影响至关重要.
研究的目的:
- 为了研究重复口服后1,4-二氧化 (DON) 毒性的分子机制.
- 分析肝脏中的基因表达变化,以确定与DON的不良影响相关的途径.
主要方法:
- 对大鼠进行了为期14天的重复剂量口服毒性测试,这些大鼠接受了不同剂量的DON.
- 进行了血液学,血液生物化学,器官重量,组织病理学和DNA微阵列基因表达分析.
主要成果:
- 病理发现包括肝脏缩,脏管状变化和垂体真空化.
- 基因表达分析揭示了与氧化应激,异生物反应,免疫反应和肝细胞癌相关的途径的丰富.
- 建议设定剂量值,因为在中剂量时没有丰富的DNA损伤反应基因,而没有肝脏病理学变化.
结论:
- 与肝癌发生相关的基因表达特征的持续改变可能表明1,4-二氧化 (DON) 的非基因毒性作用模式.
- 这些发现增强了对DON的一般毒性和癌症发生前的早期肝脏变化的理解.
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