Effects of lidamycin on genomic DNA in human heptatoma BEL-7402 cells  

力达霉素对人肝癌BEL-7402细胞基因组DNA的影响(英文)

作　　者：何琪杨[1] 姜兵 李电东[1] 

机构地区：[1]中国医学科学院中国协和医科大学医药生物技术研究所,北京中国100050

出　　处：《Acta Pharmacologica Sinica》2002年第3期253-256,共4页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China (№ 30070878) and Major State Basic Research Development Program Foundation of China (№ G2000057010).

摘　　要：To further study the effect of enediyne antibiotic lidamycin (C1027) on genomic DNA in human hepatoma BEL-7402 cells. METHODS: The DNA patterns were detected by agarose gel electrophoresis. The gene damage was revealed by Southern hybridization. The DNA repair was determined by neutral agarose gel electrophoresis. The lidamycin-cleaved sites were determined with superhelix GEM plasmid. RESULTS; The DNA “ladder” patterns were observed after the BEL-7402 cells were treated with lidamycin 1 μmol/L for 15, 30, 60 min. The extrons and introns of active N-ras gene in the BEL-7402 cells were easily damaged by lidamycin at low concentrations, but no damage in the silent IL-2 gene was observed. It was difficult to repair DNA breaks after the BEL-7402 cells were treated with lidamycin. The cleaved sites of GEM plasmid treated with lidamycin were -OH HO-. CONCLUSION-. Lidamycin can significantly damage genomic DNA in the hepatoma BEL-7402 cells. The results make it helpful to elucidate the molecular mechanism of potent cytotoxicities of lidamycin to tumor cells.目的:深入研究力达霉素对人肝癌BEL-7402细胞基因组DNA的影响.方法:琼脂糖凝胶电泳检测DNA泳带;Southern杂交检测对基因的损伤;中性凝胶电泳检测DNA断裂修复;超螺旋GEM质粒检测断裂DNA位点.结果:力达霉素1μmol/L处理BEL-7402细胞15、30、60min,可检测到明显的DNA梯带.低浓度的力达霉素对活跃基因N-ras的外显子和内含子均有明显的损伤作用,但对沉默IL-2基因没有影响.力达霉素断裂DNA后,DNA损伤难以修复.力达霉素断裂GEM质粒DNA的位点是-OH HO-.结论:力达霉素明显地损伤人肝癌BEL-7402细胞的基因组DNA.该结果有助于解释其高活性地杀伤肿瘤细胞的分子机制.

关 键 词：LIDAMYCIN antineoplastic agents DNA damage ras genes HEPATOMA 

分 类 号：R735.7[医药卫生—肿瘤] R979.14[医药卫生—临床医学]