Metaphase poisoning

The contractile proteins of the spindle apparatus must draw apart the replicated chromosomes before the cell can divide. This process is prevented by the so-called spindle poisons (see also colchicine, p. 316) that arrest mitosis at metaphase by disrupting the assembly of microtubules into spindle threads. The vinca alkaloids, vincristine and vinblastine (from the periwinkle plant. Vinca rosea) exert such a cell-cycle-specific effect. Damage to the nervous system is a predicted adverse effect arising from injury to microtubule-operated axonal transport mechanisms. 

Colchicine is a specific spindle poison, which binds to tubulin, and inhibits its polymerization. Consequently, colchicine blocks mitosis, causing aneuploidy, the unequal partition of chromosomes, and metaphase arrest. 

Marrazzini, A., Betti, C., Bernacchi, F., Barrai, I. Barale, R. (1994b) Mieronueleus test and metaphase analyses in mice exposed to known and suspected spindle poisons. Mutagenesis, 9, 505-515... 

Griseofulvin is a mitotic spindle poison. In vitro, ii rapidly arrests cell divirsion in metaphase. It causes a rapid, reversible dissolution of the mitotic spindle apparatus, ably by binding with the tubulin dimer that is required for microtubule assembly. The selective toxicity to fungi o probably due to the propensity of the drug to concentrate in ti.ssues rich in keratin, where dermatophytes typically cstalv li.sh infections. 

Narciclasine, an alkaloid isolated from the bulbs of narcissus, possesses antimitotic activity against S-180 in ascites form suggesting thereby that it acts essentially as a metaphasic or preprophasic poison. 

A drastic decrease in the number of mitoses was observed two hours after subcutaneous injection of 0-9 mg/kg of the drug, and after four hours no more mitotic figures were detected. Analysis of the antimitotic effect has suggested that narciclasine acts essentially as a metaphasic or preprophasic poison [129]. Spectroscopic analysis and chemical transformation have... 

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