CELL-CYCLE EFFECTS OF CC-1065

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (9) , 4227-4232
Abstract
To determine phase-specific toxicity, synchronous CHO [Chinese hamster ovary] cultures were started from mitotic cells harvested after colcemid pretreatment. Mitotic cells were the most sensitive, and sensitivity decreased as the cells progressed through G1 to S and G2. Experiments with B16 [mouse melanoma] and CHO mitotic cells harvested without Colcemid pretreatment also showed that mitotic cells were more sensitive than G1/S-phase cells. Cell progression studies showed that CC-1065 did not affect progression from mitotsis to G1 or from G1 to S. Cells progressed slowly through S at low levels (1 ng/ml) of the drug but were blocked in S at 5 ng/ml. Cell progression from G2 to M was blocked by CC-1065. DNA synthesis in B16 cells was measured at different times after 2-h exposure to CC-1065. The percentage of inhibition of DNA synthesis was minimum at 4 h and maximum at 19 h after drug exposure. Since B16 cell progression studies showed a marked change in percentage of S-phase cells during this time, the DNA synthesis rate was calculated as cpm/s-phase cell. After this correction (i.e, expressing DNA synthesis as cpm/S-phase cell), the percentage of inhibition of DNA synthesis was minimum at 0 h and gradually increased to maximum inhibition at 19 h without the decrease seen previously at 4 h.

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