Effects of lidamycin on genomic DNA in human hepatoma BEL-7402 cells.
OBJECTIVE
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 micromol/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-.


CONCLUSIONS
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.
He
Qi-Yang
QY
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
Jiang
Bing
B
Li
Dian-Dong
DD
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics; D053281:Enediynes; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D053281:Enediynes; C058024:C 1027