双向表观遗传毒性测定用于评估化学诱导的表观遗传效应,利用家政TK基因
Haruto Yamada1, Mizuki Odagiri1, Keigo Yamakita1
1Department of Biology, Graduate School of Science, Chiba University, Chiba, 263-8522, Japan.
Scientific reports
|March 5, 2025
概括
这项研究引入了一种新的检测方法,用于检测使用记者基因的化学诱导的表观遗传变化. 该试验量化了表观遗传变化的增加和减少,有助于评估致癌物质风险.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 化学物质可以通过表观遗传改变引起癌症.
- 家政基因可以作为全球表观遗传变化的记者位置.
- 现有的检测表观遗传变化的方法很复杂.
研究的目的:
- 为评估化学诱导的表观遗传效应开发一种简单,具有成本效益和定量报告系统.
- 用提米丁激酶 (TK) 基因突变试验作为这个新系统的基础.
- 调查这种试验在检测双向表观遗传变化的有用性.
主要方法:
- 开发了一种使用CRISPR/dCas9-SunTag-DNMT3A编辑人类淋巴细胞TK6细胞内源性TK基因的CpG促进基因位点的epi-genotoxicity测试.
- 利用修改后的mtk6细胞来量化化学诱导的表观遗传效应.
- 采用染色体免疫沉和西部涂抹来分析分子变化.
主要成果:
- 该试验成功检测出由DNA甲基转移酶 (DNMT) 抑制剂 (5-Aza-2'-deoxycytidine和GSK-3484862) 诱导的TK逆转率增加.
- 该试验首次证明了非遗传毒性致癌物12-O-tetradecanoylphorbol-13-acetate (TPA) 引起的TK逆转频率显著降低.
- 治疗TPA导致H3K27Ac水平的总体下降,这可能是由于TPA介导的炎症.
结论:
- 开发的经遗传毒性试验是量化化学诱导表观遗传效应的宝贵工具.
- 该检测可以检测表观遗传标记的增加和减少,提供化学物质暴露的全面评估.
- 该方法有助于评估由化学物质暴露引发的双向表观遗传变化,有助于评估致癌物质风险.
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