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

Can J Biochem Cell Biol. 1985 Jun;63(6):503-10. doi: 10.1139/o85-069.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Clone Cells
  • Cricetinae
  • Cricetulus
  • Drug Resistance
  • Female
  • Maytansine / pharmacology*
  • Mutation*
  • Ovary
  • Oxazines / pharmacology*
  • Peptide Fragments / analysis
  • Proteins / isolation & purification
  • Puromycin / pharmacology
  • Tubulin / genetics*
  • Tubulin / isolation & purification

Substances

  • Oxazines
  • Peptide Fragments
  • Proteins
  • Tubulin
  • Maytansine
  • Puromycin