Epidermla cell kinetics in hairless mice after bleomycin. I. Perturbations after different single doses

Three different doses of bleomycin (BLM) (2,1, and 0.01 mg/animal) were injected ip into groups of hairless mice. Cell kinetic alterations in the basal layer of the epidermis were studied up to 10 days after BLM administration. The two highest doses of BLM affected the epidermal cell kinetics in a similar way but with different time courses. Only a moderate depression of the labeling index was observed during the first 24 hours. The results indicate that cells affected by BLM in the middle of the G1 phase are arrested in their subsequent S phase, and that thereafter an increase in the rate of DNA synthesis may occur in the arrested cells without increasing the number of cells in S phase. The percentage of cell accumulated in S and G2 phases as determined by flow cytofluorometry never exceeded 130% of control values with any of the doses. Phase durations were determined from percentage of labeled mitoses curves after the highest dose of BLM and were not significantly different from normal values, indicating that the accumulated cels are probably out of cycle and unable to proliferate again. Calculations based on cell counts and mitotic rate showed that the cells had a prolonged lifespan. No block and subsequent release of cells specifically caused by BLM were observed. BLM has a complex effect on the epidermis, and therefore does not seem to be a promising agent for cell synchronization as a basis for combination chemotherapy in vivo.