Maytansine-resistant mutants of Chinese hamster ovary cells with an alteration in alpha-tubulin.


Mutant clones of Chinese hamster ovary cells resistant to killing by the Vinca alkaloid maytansine have been isolated using a single-step procedure. These mutants are threefold more resistant to killing by the drug than the wild-type parent. The majority of the clones (30 to 34) probably contain alterations in membrane permeability based on their cross-resistance to an unrelated drug, puromycin. Two of the four puromycin-sensitive clones were found to contain "extra" spots which migrated close to alpha-tubulin on two-dimensional gels. The "extra" spots were shown to be electrophoretic variants of alpha-tubulin with an identical two-dimensional tryptic peptide map to that of the wild-type alpha-tubulin. The alpha-tubulin mutants were cross-resistant to other microtubule disrupting drugs such as griseofulvin, vinblastine, and colcemid, but were more sensitive to the microtubule-stabilizing agent taxol than the wild-type parental cells. Mutant--wild-type hybrids were found to be resistant to levels of maytansine intermediate between the lethal doses for mutant and wild-type cells. A possible explanation for the drug resistance of these mutants is discussed.

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@article{Schibler1985MaytansineresistantMO, title={Maytansine-resistant mutants of Chinese hamster ovary cells with an alteration in alpha-tubulin.}, author={Matthew J. Schibler and Fernando Cabral}, journal={Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire}, year={1985}, volume={63 6}, pages={503-10} }