The induction of polyploidy in continually cycling cultured cells may induce genetic instability in the daughter cells by facilitating the formation of viable aneuploid cells (2) and may play the same role during tumor forma

At any point during the progression of many tumor types, cells can develop a hyperploid DNA conteni Hyperploid tumors are signiflcantiy more aggressive, with a higher growth rate and a poor patient prognosis. Yeast genetics have implicated three important genes Involved in DNA ploidy changes: cdc2, cycin b, and a specific inhibiter of the p34@2/cyc1in B kinase, rumi. Mutations in these genes uncoupled the dependence of mlttsis on DNA replication in the fission yeast, Saccharomyces pombe. It was proposed that the inactivation of the mitotic kinase complex, p34@2/ cydlin B, induces a G1 state wherein the cells re-replicate their DNA without an intervening mitosis. We show in this report that treatment of only M phase-arrested mouse cells, with the protein kinase inhibitor stauros@ne, induced polyploidy. Nocodazole-arrested metaphase FF210 cells were pulsed with 100 ng/ml of staurosporine for 1 h. This 1-h treatment results in the inhibition of the mitotic p34@ kinase. The inhibition ofthe mitotic kinases leads to a reduction in the histone Hi and H3 mitotic-associated phosphorylations, chromosome decondensation, and nuclear membrane reformation. When released into normal growth medium, these cells are reset to a G1 state, re-replicate their DNA without completing InItOSiS, and become octaploid.