1987 Volume 78 Issue 10 Pages 1121-1127
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 100ng/ml SN-07 for 1hr and surviving colonies were counted after a 14-day incubation. It was found that 500ng/ml SN-07 inhibited both RNA and DNA syntheses significantly at 40 and 80min, respectively, while 8, 000ng/ml did not affect protein synthesis at 80min. Treatment with a low concentration (80ng/ml) of SN-07 for 1hr inhibited both RNA and DNA syntheses after a 24-hr post-incubation. The alkaline elution technique revealed that 8, 000ng/ml SN-07 induced DNA interstrand cross-links time-dependently for 1 to 4hr, and a 1-hr treatment with 80 to 8, 000ng/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 (25ng/ml) of SN-07, and typical inhibition of the cell cycle progression was observed at a cytocidal concentration (200ng/ml).
