The mechanism of action of quinocarmycin citrate (KW 2152) on mouse L1210 cells in vitro

The effects of the antitumor antobiotic, quinocarmycin citrate (KW 2152), on L1210 cells were studied in vitro. The cellular growth was completely inhibited at 10^-6M KW 2152, and after 2 days no viable cell was seen. The incorporation fo ³H-thymidine, ³H-uridine, or ³H-leucine into the acid-insoluble fraction was not affected at 10^-4M for 1 h; however, when the cells were treated with 10^-6M for 24 h, the radioactivity appearing in the acid-insoluble fraction was reduced to 20%, 30%, and 48%, respectively, of the control. The single strand scission of the DNA of L1210 cells was seen at 10^-7M for 24 h, as revealed by an alkaline, sucrose density gradient. However, no damage to plasmid pBR322 was observed even at 10^-6M KW 2152 for 24 h, as revealed by 0.8% agarose gel electrophoresis, indicating that some soluble factors of the cells might contribute to the damage to the DNA of L1210 cells. The processing of pre-rRNA of the cells was not inhibited at 10^-6M of the drug for 24 h of incubation.