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Heterogeneity in the Mitotic Checkpoint Control of BALB/3T3 Cells and a Correlation with Gene Amplification Propensity¹

Department of Biological Sciences, Stanford University, Stanford, California 94305

Chinese hamster ovary (and many rodent cell lines) transiently delay mitosis and progress into a second cell cycle without undergoing cytokinesis when treated with Colcemid, whereas HeLaS3 (and most human cell lines) arrest permanently in mitosis. We have discussed these differences and their consequences for cell survival under cell cycle-perturbing conditions within the context of mitotic checkpoint control (Schimke et al., Cold Spring Harbor Symp. Quant. Biol., 56: 417–425, 1991). Here, we report studies with mouse BALB/3T3 cell populations which, by the criterion of response to Colcemid, constitute a heterogeneous population with respect to mitotic checkpoint control. Clonal and subclonal populations retain population heterogeneity but with a bias for enrichment of cell populations that respond as do HeLaS3 cells. We have analyzed clones for their propensity for gene amplification as assessed by a stepwise increment selection protocol in methotrexate and report that there are significant differences in amplification propensities that correlate with differences in mitotic checkpoint control properties.

¹ Supported by research grants from the National Institute of General Medical Sciences (GM14931) and the National Cancer Institute (CA16831).

² To whom requests for reprints should be addressed.

Received 9/14/93. Accepted 8/ 5/94.

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