Mechanisms of action of a novel macromolecular antitumor antibiotic, SN-07, on mouse leukemia L1210 cells in culture.
The mechanisms of action of a novel macromolecular antitumor antibiotic (SN-07) were examined using cultured mouse lymphoid leukemia L1210 cells. A shoulder exponential-type cytotoxicity was observed when the cells were treated with 3.13 to 100 ng/ml SN-07 for 1 hr and surviving colonies were counted after a 14-day incubation. It was found that 500 ng/ml SN-07 inhibited both RNA and DNA syntheses significantly at 40 and 80 min, respectively, while 8,000 ng/ml did not affect protein synthesis at 80 min. Treatment with a low concentration (80 ng/ml) of SN-07 for 1 hr inhibited both RNA and DNA syntheses after a 24-hr post-incubation. The alkaline elution technique revealed that 8,000 ng/ml SN-07 induced DNA interstrand cross-links time-dependently for 1 to 4 hr, and a 1-hr treatment with 80 to 8,000 ng/ml SN-07 induced DNA breaks after a 24-hr post-incubation. According to flow cytometric analysis, most L1210 cells progressed to the G2 phase in the cell cycle at a cytostatic concentration (25 ng/ml) of SN-07, and typical inhibition of the cell cycle progression was observed at a cytocidal concentration (200 ng/ml).
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D009279:Naphthacenes / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D009279:Naphthacenes; D012334:RNA, Neoplasm; C047795:SN-07