Epidermal cell kinetics in hairless mice after bleomycin. II. Perturbations after multiple doses.

Bleomycin (BLM) at doses of 0.1 mg/animal was injected into hairless mice every 4 hours for 4 days. Epidermal cell cycle phase distributions were determined by flow cytofluorometric DNA measurements. Labeling indices and mean grain counts were determined by means of autoradiography, and mitotic rates were determined by demecolcine arrest of metaphases. A small, partially reversible accumulation of cells with G2 phase DNA content was observed subsequent to BLM administration. Most of the cells accumulated in G2 phase, however, seemed to stop proliferation and die in this phase. Thus, BLM does not fulfill the criteria for a good synchronizing agent in the hairless mouse epidermis. Flow cytofluorometry alone cannot determine whether piling up of cells in a particular cell cycle phase is true synchrony or an accumulation of lethally damaged cells. Several cell kinetic methods should be used to demonstrate real synchrony.