Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells.

Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells.
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DOI:
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发表时间:
1991-11
期刊:
影响因子:
11.2
通讯作者:
M. Agarwal;M. Clay;E. J. Harvey;H. H. Evans-H.;A. Antunez;N. Oleinick
M. Agarwal;M. Clay;E. J. Harvey;H. H. Evans-H.;A. Antunez;N. Oleinick
中科院分区:
医学1区
文献类型:
--
作者:
M. Agarwal;M. Clay;E. J. Harvey;H. H. Evans-H.;A. Antunez;N. Oleinick

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用酞菁铝敏化两株小鼠淋巴瘤L5178 Y细胞,研究其光动力学疗法(PDT)后的细胞死亡方式。菌株LY-R和LY-S不同,其相对敏感性UVC辐射,X-辐射,和PDT,都响应PDT经历细胞凋亡。DNA被降解成长度为约180-190个碱基对的倍数的片段(即,细胞凋亡的生化标志物。DNA片段化是剂量和时间依赖性的,这表明该反应是与细胞杀伤相关的酶促过程。蛋白质合成抑制剂放线菌酮和RNA合成抑制剂放线菌素D增强了核酸内切酶的DNA断裂。透射电子显微镜显示染色质凝聚周围的核,这也是细胞凋亡的特征。PDT诱导L5178 Y细胞凋亡是迅速的,与DNA的发生在短短30分钟的显着降解。PDT的反应的快速性表明,PDT产生的细胞损伤可以直接激活核酸内切酶和染色质凝聚,从而绕过许多早期步骤的信号转导程序是由其他代理引起凋亡。
The mode of cell death of two strains of mouse lymphoma L5178Y cells was studied following photodynamic therapy (PDT) sensitized by chloroaluminum phthalocyanine. Strains LY-R and LY-S differ in their relative sensitivities to UVC radiation, X-radiation, and PDT; both responded to PDT by undergoing apoptosis. The DNA was degraded into fragments with lengths which are multiples of approximately 180-190 base pairs (i.e., oligonucleosome size), a biochemical marker of apoptosis. The DNA fragmentation was dose and time dependent which indicates this response to be an enzymic process related to cell killing. Cycloheximide, a protein synthesis inhibitor, and actinomycin D, an RNA synthesis inhibitor, enhanced the endonucleolytic DNA fragmentation. Transmission electron microscopy revealed chromatin condensation around the periphery of the nucleus, which is also characteristic of apoptosis. The induction of apoptosis in L5178Y cells by PDT was rapid, with marked degradation of DNA occurring in as little as 30 min. The rapidity of the response to PDT suggests that cellular damage produced by PDT can directly activate endonucleolysis and chromatin condensation, thereby by-passing many of the early steps in the signal transduction program which are acted upon by other agents causing apoptosis.