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CC1065 (NSC 298223), a Most Potent Antitumor Agent: Kinetics of Inhibition of Growth, DMA Synthesis, and Cell Survival

CC1065 (NSC 298223), a Most Potent Antitumor Agent: Kinetics of Inhibition of Growth, DMA Synthesis, and Cell Survival,Bijoy K. Bhuyan,Kenneth A. Newe

CC1065 (NSC 298223), a Most Potent Antitumor Agent: Kinetics of Inhibition of Growth, DMA Synthesis, and Cell Survival   (Citations: 13)
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CC-1065 (NSC 298223) is the most cytotoxic agent tested against cells in culture in our laboratory. The 50% lethal doses for exponentially growing B16 melanoma and Chinese hamster ovary cells were 0.44 and 0.14 ng/ml, respectively, as com pared to 35 and 500 ng/ml for Adriamycin. In the human tumor-cloning assay, 1-hr exposure to CC-1065 (0.1 ng/ml) caused ^50% lethality in a broad spectrum of tumors. The dose-survival curves for B16 and Chinese hamster ovary cells were characterized by an initial shoulder followed by an ex ponential decline with increasing dose. CC-1065 was more lethal to exponentially growing B16 cells (50% lethal dose = 0.44 ng/ml) than to plateau-phase cells (50% lethal dose = 1.2 ng/ml). CC-1065 inhibited DNA synthesis much more than did RNA or protein synthesis. After a 2-hr incubation with drug, inhibition of DNA synthesis was low immediately (0 hr) after drug expo sure and reached maximum inhibition about 20 hr 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).
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    • ...exposure was determined by a colony formation assay (20)...
    • ...Linbro plates. Plates were incubated for colony formation, and the colonies were stained and counted (20)...

    Bijoy K. Bhuyanet al. Multidrug Resistance Is a Component of V79 Cell Resistance to the Alky...

    • ...After drug exposure, cell monolayers were washed with medium and harvested, and cell survival determined by a colony forming assay as previously described (11,12)...

    B. K. Bhuyanet al. Lethality, DNA Alkylation, and Cell Cycle Effects of Adozelesin (U-739...

    • ...CC-1065 and its CPP containing analogues are therapeutically active against a variety of experimental tumors (2-6); however, CC-1065 itself was found to cause a lethal delayed toxicity in mice at therapeutic doses which precluded its clinical development (5)...
    • ...Lack of efficient repair would explain the in vivo longevity of the CPI adduct (19), inhibition of DNA synthesis observed in cultured cells (3), and the acute cytotoxicity (3, 4) displayed by these compounds...
    • ...Lack of efficient repair would explain the in vivo longevity of the CPI adduct (19), inhibition of DNA synthesis observed in cultured cells (3), and the acute cytotoxicity (3, 4) displayed by these compounds...

    Thomas J. Monroeet al. In Vivo Mutagenesis Induced by CC1065 and Adozelesin DNAAlkylation in ...

    • ...This agent is one of the most cytotoxic antitumor agents known and is active against several experimental murine tumors in vivo(4- 6). CC-1065 was 100 times more potent than Adriamycin against a broad spectrum of human tumors in the cloning assay (5, 6)...
    • ...This agent is one of the most cytotoxic antitumor agents known and is active against several experimental murine tumors in vivo(4- 6). CC-1065 was 100 times more potent than Adriamycin against a broad spectrum of human tumors in the cloning assay (5, 6)...
    • ...Previous studies by Bhuyan et al. (5) and Li et al. (6) showed that CC-1065 was about 50-1000 times more cytotoxic to B16 melanoma and LI210 cells in culture than Adriamycin and actinomycin D, and it inhibited DNA synthesis much more than it inhibited RNA or protein synthesis...
    • ...of several of the analogs is shown in Fig. 2. As previously reported for B16 cells, the lethality of CC-1065 did not increase when exposure was increased from 2 to 24 h (5)...

    Earl G. Adamset al. Effects of U-71,184 and Several Other CC1065 Analogues on Cell Surviva...

    • ...This agent is one of the most cytotoxic antitumor agents known and is active against several experimental murine tumors in vivo(2, 3). CC-1065 was 100 times more potent than Adriamycin against a broad spectrum of human tumors in the human tumorcloning assay (4)...
    • ...Previous studies by Bhuyan et al. (4) and Li et al. (5) showed that CC-1065 was about 50-1000 times more cytotoxic to B16 melanoma and LI210 cells in culture than Adriamycin and actinomycin D, and inhibited DNA synthesis much more than it inhibited RNA or protein synthesis...

    Philip R. Harbachet al. Mutagenicity of the Antitumor Antibiotic CC1065 and Its Analogues in M...

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