CC-1065 (NSC-298223), A MOST POTENT ANTI-TUMOR AGENT - KINETICS OF INHIBITION OF GROWTH, DNA-SYNTHESIS, AND CELL-SURVIVAL

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (9) , 3532-3537
Abstract
CC-1065 (NSC 298223) is the most cytotoxic agent tested against cells in culture in the authors'' laboratory. LD50 for exponentially growing B16 melanoma and Chinese hamster ovary (CHO) cells is 0.44 and 0.14 ng/ml, respectively, as compared to 35 and 500 ng/ml for adriamycin. In the human tumor-cloning assay, 1-h exposure to CC-1065 (0.1 ng/ml) caused .gtoreq. 50% lethality in a broad spectrum of tumors. The dose-survival curves for B16 and CHO cells were characterized by an initial shoulder followed by an exponential decline with increasing dose. CC-1065 was more lethal to exponentially growing B16 cells (LD50 = 0.44 ng/ml) than to plateau-phase cells (LD50 = 1.2 ng/ml). CC-1065 inhibited DNA synthesis much more than did RNA or protein synthesis. After a 2-h incubation with drug, inhibition of DNA synthesis was low immediately (0 h) after drug exposure and reached maximum inhibition about 20 h later. The doses for 50% inhibition of growth (0.18 ng/ml), survival (0.44 ng/ml), and DNA synthesis (0.15 ng/ml) were in the same range, whereas RNA synthesis was inhibited 50% at a much higher dose (5 ng/ml).

This publication has 1 reference indexed in Scilit: