Cell Cycle Specificity of Certain Antimicrotubular Drugs in Schizosaccharomyces pombe

Abstract

Of the 7 antimicrotubular drugs tested, nocodazole, mebendazole and trifluralin at saturable concentrations failed to inhibit cell division in S. pombe, while carbendazim, thiabendazole and chloropropham each at 50 .mu.g ml-1 and amiprophos methyl at 200 .mu.g ml-1 completely arrested cell division. This inhibition was associated with striking morphological changes in which carbendazim- and thiabendazole-treated cells became elongated and pseudohyphal, whereas chloropropham- and amiprophos methyl-treated cells appeared small and rounded with occasional V-shaped pairs. Lomofungin staining revealed that nuclear division was arrested by these drugs. Suspected blockage of defined cell cycle stages was confirmed by pulse-induction experiments which revealed that cells could be synchronized into division using exposure to a drug for 1 generation. Experiments with synchronous cultures prepared by size selection showed that different drugs possessed different transition points; carbendazim and thiabendazole were effective in blocking a late stage of the cell cycle just prior to division, whereas amiprophos methyl affected a very early stage. Evidently some of the drugs used exert cell cycle specificity in S. pombe either by impairing microtubule assembly mechanisms (as with carbendazim and thiabendazole) or by inhibiting synthesis of tubulin subunits (as with amiprophos methyl). These drugs could prove useful in studies of microtubule biogenesis during the cell cycle in yeast.