Bleomycin effect on DNA replication and proliferation kinetics using Ehrlich ascites tumor as a model]

The effect of the cytostatic agent bleomycin isolated from Streptomyces verticillus on DNA-synthesis and cell cycle of hyperidiploid Ehrlich-Lettré ascites tumor was studied in vivo and in vitro by means of liquid scintillation counting and pulse cytophotometry. A highly significant and dose dependent inhibition of 3H-thymidine incorporation into the tumor cells in vitro could be found. This inhibition of DNA-synthesis results in vivo in an initial decrease of cells in the S and (G9 plus M) phase in the DNA histogram. A partial synchronization of the tumor can be shown using 12.5, 25.0 and 50.0 mg/kg body weight of bleomycin. At a dose of 12.5 mg/kg body weight bleomycin, two subpopulations which pass through the cell cycle partially synchronized at a time interval of four hours, can be discriminated. This effect declines after the passage through one cell cycle. After 120 h most of the cells are in G1-area, another compartment in the late S-area and the smallest compartment in the (G2 plus M)-area of the DNA histogram. The arrest in the late S-area probably is the consequence of damage to the DNA synthetizing apparatus: DNA-synthesis cannot be completed and G2 cannot be reached. The significance of investigations concerning proliferation kinetics for tumor therapy is pointed out.