Department of Biochemistry, J.N. Medical College, Aligarh Muslim University, Aligarh, 202002, U.P., India.
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, U.P., India.
Int J Biol Macromol. 2018 Jan;106:551-558. doi: 10.1016/j.ijbiomac.2017.08.051. Epub 2017 Aug 12.
Hypochlorous acid (HOCl) is generated by activated phagocytes at the site of inflammation. Exposure of DNA to HOCl results in base and nucleotide modifications causing DNA damage, which is one of the leading causes of various pathological conditions including carcinogenesis. In the present work, various biophysical techniques were used to study HOCl induced structural and conformational changes in human placental DNA. The HOCl modified DNA showed hyperchromicity, reduced fluorescence and decrease in melting temperature. Circular dichorism (CD) and Fourier transform infra-red (FT-IR) studies exhibited conformational changes and shift in band positions of DNA, respectively, suggesting structural changes. Agarose gel electrophoresis and scanning electron microscopy showed strand breakage and decreased aggregation. These results suggest that HOCl causes conformational and structural perturbations in mammalian DNA, which may consequentially lead to DNA mutations resulting in perturbation of epigenetic signals leading to cancer and autoimmune diseases.
次氯酸(HOCl)是由炎症部位的活化吞噬细胞产生的。DNA 暴露于 HOCl 会导致碱基和核苷酸修饰,从而导致 DNA 损伤,这是包括致癌在内的各种病理状况的主要原因之一。在本工作中,使用各种生物物理技术研究了 HOCl 诱导的人胎盘 DNA 的结构和构象变化。HOCl 修饰的 DNA 表现出增色效应、荧光降低和熔点降低。圆二色性(CD)和傅里叶变换红外(FT-IR)研究分别显示了 DNA 的构象变化和带位置的移动,表明了结构的变化。琼脂糖凝胶电泳和扫描电子显微镜显示了链断裂和聚集减少。这些结果表明,HOCl 会导致哺乳动物 DNA 的构象和结构扰动,这可能导致 DNA 突变,从而破坏表观遗传信号,导致癌症和自身免疫性疾病。