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在人性化的肝脏小鼠中,4,4'-甲基2-氨) 的尿囊致癌潜力
Shugo Suzuki1, Min Gi1,2, Takuma Kobayashi3
1Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan.
Toxicological sciences : an official journal of the Society of Toxicology
|September 17, 2024
概括
职业接触4,4'-甲基二2-乙烯 (MOCA) 会增加膀癌的风险. 人性化肝脏小鼠显示MOCA诱导的泌尿器损伤和更高的N-OH-MOCA水平,表明其在人类致癌过程中的作用.
科学领域:
- 毒理学 毒理学 毒理学
- 致癌的发生是致癌的产生.
- 代谢过程中的代谢.
背景情况:
- 职业暴露于4,4'-甲基2-氨 (MOCA) 与增加尿膀癌风险有关.
- 了解MOCA的代谢途径对于评估其致癌潜力至关重要.
研究的目的:
- 用人性化肝脏小鼠模型研究MOCA代谢在膀癌发生中的作用.
- 为了比较MOCA诱导的尿囊表皮和代谢物形成在人性化的肝脏与非人性化的小鼠.
主要方法:
- 给非人性化 (F1-TKm30) 和人性化肝脏小鼠4周和28周的MOCA.
- 对MOCA诱导的代谢酶表达,代谢物形成和尿路效应的变化进行比较.
- 分析尿中的代谢物度,特别是N-OH-MOCA.
主要成果:
- 人性化肝脏小鼠在MOCA暴露4周后表现出尿路细胞增生,增殖和DNA损伤,与非人性化小鼠不同.
- 在4周后,人性化肝脏小鼠的尿液N-OH-MOCA度比非人性化小鼠高10倍以上.
- 在两个模型之间观察到细胞染色体P450异型表达的明显差异.
结论:
- 建议N-OH-MOCA是MOCA在人类中的致癌潜力的重要贡献者.
- 人性化肝脏小鼠模型有效地模仿了MOCA诱导的早期膀组织变化,与人类暴露相关.
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