Higuchi Yoshiro, Mizukami Yuji, Yoshimoto Tanihiro
Department of Molecular Pharmacology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Ann N Y Acad Sci. 2003 Dec;1010:326-30. doi: 10.1196/annals.1299.058.
Giant DNA fragments (1-2 Mbp) were found in C6 rat glioma cells irradiated by a lethal dose of ultraviolet-C (UV-C, 254 nm) at 50 J/m(2). After irradiation, the fragments mutated into high-molecular-weight (100-800 kbp) DNA fragments and then into ladder-formed internucleosomal DNA fragments. Poly-ADP-ribose polymerase (PARP) activity and NAD levels were reduced during DNA fragmentation. Some inhibitors of caspase and protease inhibited DNA ladder formation, but not giant DNA fragmentation, whereas antioxidants did not inhibit DNA fragmentation. These results suggest that a lethal dose of UV radiation induces giant DNA fragmentation and leads to internucleosomal DNA fragmentation associated with apoptosis through some caspases and nonreactive oxygen species in cells.
在接受50 J/m²致死剂量的紫外线C(UV-C,254 nm)照射的C6大鼠胶质瘤细胞中发现了巨大的DNA片段(1-2 Mbp)。照射后,这些片段突变为高分子量(100-800 kbp)的DNA片段,然后变为阶梯状的核小体间DNA片段。在DNA片段化过程中,聚ADP-核糖聚合酶(PARP)活性和NAD水平降低。一些半胱天冬酶和蛋白酶抑制剂可抑制DNA梯状条带的形成,但不抑制巨大DNA片段化,而抗氧化剂则不抑制DNA片段化。这些结果表明,致死剂量的紫外线辐射会诱导巨大DNA片段化,并通过细胞中的一些半胱天冬酶和非活性氧物种导致与细胞凋亡相关的核小体间DNA片段化。