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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.