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

Aim: 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-.

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.