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Accumulation of Human Promyelocytic Leukemia (HL-60) Cells at Two Energetic Cell Cycle Checkpoints¹

Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre and Department of Pathology, McMaster University, Hamilton, Ontario, L8N 3Z5 Canada

Agents that disrupt mitochondrial function were used to monitor the contribution of ATP to cell cycle progression. Following nontoxic exposure to these agents, flow cytometric analysis of the cell population showed a significant increase in the proportion of cells in G₁ at low doses of the agent and in G₂-M at higher doses, in accordance with the degree of ATP reduction induced by the compound. These data indicate that cycling cells must maintain a minimal ATP content to satisfy the energy requirement of the checkpoint that allows passage through G₁ into S phase. Once committed, successful passage through G₂ into mitosis is also conditional upon maintenance of a critical ATP content sufficient to satisfy the second energy-sensitive checkpoint that exists at this transition. These data establish a foundation for future investigations into the energy dependence of cell cycle events and propose novel means for cell cycle intervention.

¹ This work was supported by Grant MA-8509 from the Medical Research Council of Canada (to G. S.) and a Medical Research Council of Canada Studentship (to S. S.).

² To whom requests for reprints should be addressed: Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario, L8V 5C2 Canada.

Received 9/ 5/95. Accepted 10/ 5/95.

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