染色体在长期内影响基因表达和DNA甲基化 在A549细胞的体外实验中
Franziska Fischer1, Sandra Stößer1, Lisa Wegmann1
1Department of Food Chemistry and Toxicology, Institute of Applied Biosciences (IAB), Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany.
International journal of molecular sciences
|September 28, 2024
概括
长期暴露于A549细胞中的染色体会导致显著的DNA低甲基化,并改变基因表达,与短期暴露不同. 慢性暴露显示出与环境和职业环境相关的独特毒性概况.
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.
- 细胞生物学 细胞生物学
背景情况:
- 染色体暴露可以破坏表观遗传调节,包括DNA甲基化,影响基因表达和基因组稳定性.
- 现有的体外研究往往使用短的潜伏期,这可能不准确地反映慢性环境或职业暴露.
研究的目的:
- 调查短期和长期染色体暴露对人类腺癌A549细胞的差异性影响.
- 为了比较细胞反应,积累,细胞周期进展,DNA甲基化和基因表达在不同染色体暴露时间下.
主要方法:
- 在短期 (24小时) 和长期 (15周) 期间,A549细胞被不同度的染色体处理.
- 通过使用高通量RT-qPCR分析了细胞内积累,细胞循环停止 (G2),全球DNA甲基化水平和基因表达.
主要成果:
- 积累在短期暴露时显示时间和度依赖性,在长期暴露时达到平原.
- 短期暴露导致G2细胞循环停止,而长期低剂量暴露则没有这种情况.
- 长期暴露导致显著的,剂量依赖的全球DNA低甲基化,与短期暴露没有影响形成鲜明对比.
- 基因表达分析显示了依赖时间的变化,特别是在炎症和DNA损伤反应基因中.
结论:
- 短期和长期的染色体暴露在A549细胞中引起了不同的毒性概况.
- 长期暴露与显著的表观遗传变化有关,如DNA低甲基化和改变的基因表达模式,突出显示了它对风险评估的更大相关性.
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