DIE WIRKUNG VON BLEOMYCIN AUF DIE DNA REDUPLIKATION UND DIE PROLIFERATIONSKINETIK AM MODELL DES EHRLICH ASZITES TUMORS

The effects of the cytostatic agent bleomycin on DNA synthesis and cell cycle of hyperdiploid Ehrlich Lettre ascites tumor were studied in vivo and in vitro by liquid scintillation counting and pulse cytophotometry. A highly significant and dose dependent inhibition of ³H thymidine incorporation into the tumor cells in vitro was found. This inhibition of DNA synthesis results in vivo in an initial decrease of cells in the S and (G₂ + M) phase in the DNA histogram. A partial synchronization of the tumor was shown using 12.5, 25.0 and 50.0 mg/kg body weight of bleomycin. At a dose of 12.5 mg/kg bleomycin, two subpopulations which pass through the cell cycle partially synchronized at a time interval of 4 hr were discriminated. This effect declined after passage through one cell cycle. After 120 hr most of the cells were in the G₁ area, another compartment in the late S area and the smallest compartment in the (G₂ + M) area of the DNA histogram. The arrest in the late S area is probably due to damage to the DNA synthesizing apparatus: DNA synthesis cannot be completed and G₂ cannot be reached. The significance of investigations on proliferation kinetics for tumor therapy is pointed out.