甲磺酸乙酯(EMS),是一种广泛使用的化学诱变剂,通过将烷基插入真核细胞中的核苷酸鸟嘌呤中而引起高频种系无效突变。EMS对非整倍体基因组动力学的影响,细胞不稳定性增加,和致癌性有关的良性和恶性肿瘤的报告,但是对高级染色质结构形态变化的分子水平理解却知之甚少。这是由于在常规显微技术中缺乏足够的分辨率来观察低于衍射极限的小结构。这里,使用超分辨率径向波动,一个很大程度上支离破碎的,分解,在EMS处理HEK293A细胞后,观察到较低密度的异染色质结构,核DNA结构域没有任何变化。该结果表明,由于点突变,发生了致癌性的早期阶段。此外,还观察到溶酶体形态拉长的明显结构变化。另一方面,观察到碎片化和增加的异质种群,线粒体的细胞质占有率增加。
Ethyl methanesulphonate (EMS), is a widely used chemical mutagen that causes high-frequency germline null mutation by inserting an alkyl group into the nucleotide guanine in eukaryotic cells. The effect of EMS on the dynamics of the aneuploid genome, increased cellular instability, and carcinogenicity in relation to benign and malignant tumors are reported, but the molecular level understanding of morphological changes of higher-order chromatin structure has poorly been understood. This is due to a lack of sufficient resolution in conventional microscopic techniques to see small structures below the diffraction limit. Here, using super-resolution radial fluctuation, a largely fragmented, decompaction, and less dense heterochromatin structure upon EMS treatment to HEK 293A cells without any change in nuclear DNA domains is observed. This result suggests an early stage of carcinogenicity happened due to the point mutation. In addition, the distinct structural changes with an elongated morphology of lysosomes are also observed. On the other hand, fragmented and increased heterogeneous populations with an increased cytoplasmic occupancy of mitochondria are observed.