Demonstration of extensive chromatin cleavage in transplanted Morris hepatoma 7777 tissue: apoptosis or necrosis?
Demonstration of extensive chromatin cleavage in transplanted Morris hepatoma 7777 tissue: apoptosis or necrosis?
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发表时间：
1993-03
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通讯作者：
K. Fukuda;M. Kojiro;Jen-Fu Chiut
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作者：
K. Fukuda;M. Kojiro;Jen-Fu Chiut
细胞死亡可通过两种机制之一发生：坏死或凋亡（程序性细胞死亡）。在本文中，我们证明了移植的莫里斯肝癌7777组织中染色质广泛切割成寡核体长度片段（DNA阶梯），这表明刺激了内源性核酸内切酶活性，该活性先前被发现参与细胞凋亡过程。在该组织中还可见到许多凋亡细胞的存在，其形态学特征是细胞质浓缩和嗜碱性核片段。为了进一步区分肝脏和肝癌细胞坏死和凋亡的形态学和生化特征，设计了体内和体外实验。发生缺血性坏死的肝组织显示出明显的DNA阶梯模式，但没有显示出细胞凋亡的形态，这表明染色质分裂成寡核小体长度的片段并不局限于凋亡细胞死亡，至少在肝细胞中是这样。然而，在体外培养的McA-RH7777细胞中，DNA阶梯模式仅在表现出凋亡特征的细胞中检测到。从这两个标准（即特征形态学和DNA阶梯）来看，我们强烈建议在移植的7777组织中凋亡过程是高度激活的。基于体外实验的结果，我们认为肿瘤细胞凋亡可能代表了肿瘤细胞在不断扩大的过程中自我调节的残余尝试和/或可能是由轻度细胞损伤（如缺氧、营养缺乏或其他未知的有害因素）引起的。我们还发现，在体外，广泛的轻度损伤或刺激可诱导肝癌细胞凋亡。
Cell death may occur by either of two mechanisms: necrosis or apoptosis (programmed cell death). In this paper, we demonstrate extensive chromatin cleavage into oligonucleosome-length fragments (DNA ladder) in transplanted Morris hepatoma 7777 tissue, which is suggestive of the stimulation of an endogenous endonuclease activity previously found to be involved in the process of apoptosis. The existence of many apoptotic cells, which are morphologically characterized by condensed cytoplasm and basophilic nuclear fragments, were also seen in this tissue. In vivo and in vitro experiments were designed to further differentiate the morphological and biochemical features of necrosis and apoptosis in liver and hepatoma cells. Liver tissue undergoing ischemic necrosis showed a distinct DNA ladder pattern without demonstrating the morphology of apoptosis, indicating that chromatin cleavage into oligonucleosomal-length fragments is not confined to apoptotic cell death, at least in liver cells. In in vitro-cultured McA-RH7777 cells, however, DNA ladder pattern was detected only in cells showing characteristic morphology of apoptosis. From these two criteria (i.e., characteristic morphology and DNA ladder), it was strongly suggested that the apoptotic process is highly activated in the transplanted 7777 tissue. Based on the results obtained from in vitro experiments, it was suggested that tumor apoptosis may represent a residual attempt at autoregulation within the expanding tumor population and/or may result from mild cellular injuries such as hypoxia, nutrient deficiency, or other unknown noxious factor(s). We also showed evidence that apoptosis is inducible in hepatoma cells in vitro by a wide range of mild injuries or stimuli.