Background
Microtubules are highly dynamic assemblies of the protein tubulin. Their dynamic behaviour is crucial to mitosis, the process of chromosomal division to form new cells. Microtubule dynamics are highly regulated during the cell cycle by endogenous cellular regulators. In addition, many antimitotic drugs and natural compounds alter the polymerisation dynamics of microtubules, blocking mitosis, and consequently, inducing cell death by apoptosis [1]. The drugs bind to diverse sites on tubulin and at different positions within the microtubule, and they have diverse effects on microtubule dynamics. However, by their common mechanism of suppression microtubule dynamics, they all block mitosis at the metaphase/anaphase transition, and induce cell death. After treatment with different anti-tubulin drugs, it was also demonstrated that apoptosis occurs either in the interphase or in mitosis depending on the cell type and experimental conditions [2, 3].
The relationship between cell cycle disturbance due to the use of these agents and apoptosis is poorly understood. Insight into the binding and mode of action of most of antimitotic drugs have been obtained by the identification and mapping of mutation in appropriate resistant lines. Unfortunately, up to now there is no strong evidence about mode of action N-phenyl carbamates, effective anti-mitotic herbicides. Although, recently it was shown that phenylcarbamates and benzimidazoles, can compete for the site(s) of binding on β-tubulin. Benzimidazoles interact very specifically with different eukaryotic β-tubulin and resistance to these anti-microtubule drugs may be caused by point mutations in β-tubulin which replace Glu-198 with either Ala, Asp, Gln, Lys, Val, or Gly, or which replace Phe-200 with Tyr [4]. As it was found amino acid substitutions in position 198 of fungal β-tubulin, lead to negative cross-resistance to phenylcarbamates, but changes Phe from Leu-250, Val from Ala-165, and Ala from Thr-237 are responsible for phenylcarbamate cross-ressistance [5]. To clarify the sensitive/resistance of isopropyl-N-phenylcarbamate (IPC) resistant N. sylvestris mutants [6] to benzimidazole the influence of different concentration of nocodazole and its diverse effects on microtubule dynamics and cell cycle progression were studied. Two different apoptotic responses and patterns in control and mutant lines were found after nocodazole treatments.