MONOCYTIC DIFFERENTIATION OF HL-60 CELLS INDUCED BY POTENT ANALOGS OFVITAMIN-D-3 PRECEDES THE G(1) G(0)-PHASE CELL-CYCLE BLOCK/

Differentiation of mammalian cells is accompanied by reduced rates of proliferation and an exit from the cell cycle. Human leukemic cells HL 60 present a widely used model of neoplastic cell differentiation, and acquire the monocytic phenotype when exposed to analogs of vitamin D- 3 (VD3). The maturation process is accompanied by two blocks in the ce ll cycle: an arrest in the G(1)/G(0) phase, and a recently described G (2) + M block. In this study we have analyzed the traverse of the cell cycle phases of the well-differentiating HL60-G cells exposed to one of ten analogs of VD3, and compared the cell cycle effects of each com pound with its potency as a differentiation-inducing agent. We found t hat in general there was a good correlation between the effects of the se compounds on the cell cycle and on differentiation, but the best ce ll cycle predictor of differentiation potency was the extent of accumu lation of the cells in the G(2) compartment. All analogs induced a mar ked decrease in the mitotic index, and polynucleation of HL60 cells wa s produced, especially by compounds which were effective as inducers o f differentiation. Time course studies showed that induction of differ entiation was accompanied by a transient increase of the proportion of cells in the G(2) + M compartment, but preceded the G(1) to S, and th e G(2) compartment blocks. These studies indicate that complex changes in the cell cycle traverse accompany, but do not precede, the acquisi tion of the monocytic phenotype by HL60 cells.