Changes in microtubule organization after exposure to a benzimidazole derivative in Chinese hamster cells.
Many aneugenic compounds are known to affect one or several components of the mitotic apparatus. The mechanisms and targets of the aneuploidy-inducing activity of the benzimidazole derivative thiabendazole remain uninvestigated. In our experiments we found that thiabendazole-treated Chinese hamster cells (Cl-1) exhibited low levels of newly synthesized tubulin, indicating microtubule poisoning. In addition, microtubule growth and organization were substantially affected at mitosis. This was revealed by the reduced length of both interpolar and astral microtubules. Furthermore, thiabendazole strongly induced multipolar and asymmetric alpha-tubulin-positive metaphase spindles, characterized, however, by the absence of fragmentation of centrosome material as evaluated by anti-gamma-tubulin antibody staining. Interestingly, we found that microtubule poisoning induced by thiabendazole was qualitatively different from that of colchicine, the best known microtubule depolymerizing agent. In fact, in interphase cells colchicine was comparatively more effective than thiabendazole in promoting depolymerization of cytoplasmic microtubules. However, colchicine could not depolymerize a sub-population of stable, acetylated microtubules, which were however significantly reduced after thiabendazole exposure. In conclusion, the capability of thiabendazole to promote chromosomal malsegregation could be related to an effect on microtubule polymerization that specifically promotes formation of aberrant spindles.
Pisano
C
C
Research and Development, Sigma-Tau, Pomezia, Rome, Department of Genetics and Molecular Biology, University 'La Sapienza', Rome, Italy.
Battistoni
A
A
Antoccia
A
A
Degrassi
F
F
Tanzarella
C
C
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D000969:Antinematodal Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D007399:Interphase / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D011233:Precipitin Tests; D013827:Thiabendazole / Q000494:pharmacology; D014404:Tubulin / Q000096:biosynthesis
D000871:Anthelmintics; D000969:Antinematodal Agents; D001562:Benzimidazoles; D014404:Tubulin; C031000:benzimidazole; D013827:Thiabendazole; D003078:Colchicine