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Fig. 6. Mechanism of resistance to antimitotic drugs. Wild-type CHO cells have approximately 38% of their total tubulin in the microtubule fraction (Table 1). Alterations in tubulin that increase microtubule stability lead to increased assembly and resistance to drugs such as colcemid (Cmd) that act to destabilize microtubules. Conversely, alterations that decrease microtubule stability lead to decreased assembly and resistance to drugs such as paclitaxel (Ptx) that act to stabilize microtubules. Alterations that stabilize or destabilize microtubules too much lead to conditional lethal phenotypes such as colcemid-dependence (CmdD) or paclitaxel-dependence (PtxD), respectively. Cells with a borderline dependence phenotype (Cmd±D and Ptx±D) define the range of assembly within which microtubules function sufficiently well to allow normal cell growth. The different number of microtubules in each cell is meant to reflect qualitatively the observation that microtubule assembly increases in colcemid-resistant cells but decreases in paclitaxel-resistant cells.





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