Luokkamäki M, Servomaa K, Rytäomaa T
Laboratory of Radiobiology, Finnish Centre for Radiation and Nuclear Safety, Helsinki.
Int J Radiat Biol. 1993 Feb;63(2):207-13. doi: 10.1080/09553009314550271.
UV irradiation induces programmed death, or apoptosis, in rat chloroleukaemia cells, a process characterized by typical cell morphology, fragmentation of chromatin into units of single and multiple nucleosomes, and transcriptional activation of LINE. Our study shows that this process is initiated by very low UV doses: exposure to one minimal erythema dose (MED, about 200 J/m2), at defined wavelengths ranging from 270 to 330 nm, is sufficient. By sequencing 100 randomly selected blunt-end chromatin fragments (single and multiple nucleosomes) we observed that at an early stage of apoptosis the fragmented DNA contains a four-fold excess of both long and short interspersed nuclear retroelements (LINEs and SINEs). A distinct sequence finding was also the observation that fragmented DNA is very rich in microsatellites, (CA)n dinucleotides in particular, and in long stretches of homopurine/homopyrimidine domains. The present results thus indicate that chromatin fragmentation in UV-induced apoptosis begins at non-random locations involving non-B DNA conformation, and that the onset of the suicide process in chloroleukaemia cells is surprisingly sensitive to UV exposure.
紫外线照射可诱导大鼠氯白血病细胞发生程序性死亡或凋亡,这一过程的特征为典型的细胞形态、染色质断裂成单个和多个核小体单位以及长散在核元件(LINE)的转录激活。我们的研究表明,这一过程由极低的紫外线剂量引发:在270至330纳米的特定波长下,暴露于一个最小红斑剂量(MED,约200 J/m²)就足够了。通过对100个随机选择的平端染色质片段(单个和多个核小体)进行测序,我们观察到在凋亡早期,断裂的DNA中长散在核元件和短散在核元件(LINEs和SINEs)的含量均多出四倍。一个独特的序列发现还包括观察到断裂的DNA富含微卫星,尤其是(CA)n二核苷酸,以及长链的同嘌呤/同嘧啶结构域。因此,目前的结果表明,紫外线诱导凋亡过程中的染色质断裂始于涉及非B型DNA构象的非随机位置,并且氯白血病细胞自杀过程的起始对紫外线暴露出奇地敏感。