Mitosis colchicine

The influences of herbicides on cell division fall into two classes, ie, dismption of the mitotic sequence and inhibition of mitotic entry from interphase (G, S, G2). If ceU-cycle analyses indicate increases in abnormal mitotic figures, combined with decreases in one or more of the normal mitotic stages, the effect is upon mitosis. Mitotic effects usually involve the microtubules of the spindle apparatus in the form of spindle depolymerization, blocked tubulin synthesis, or inhibited microtubule polymerization (163). Alkaloids such as colchicine [64-86-8J,viahla.stiae [865-21-4] and vincristine [57-22-7] dismpt microtubule function (164). Colchicine prevents microtubule formation and promotes disassembly of those already present. Vinblastine and vincristine also bind to free tubulin molecules, precipitating crystalline tubulin in the cytoplasm. The capacities of these dmgs to interfere with mitotic spindles, blocking cell division, makes them useful in cancer treatment. 

DCPA inhibits the growth of grass species by dismpting the mitotic sequence, probably at entry (190). DCPA influences spindle formation and function (181) and causes root-tip swelling (182) and britde shoot tissue (191). It has been reported that DCPA, like colchicine and vinblastine, attests mitosis at prometaphase and is associated with formation of polymorphic nuclei after mitotic arrest (192). Pronamide also inhibits root growth by dismpting the mitotic sequence in a manner similar to the effect of colchicine and the dinitroanilines (193,194). Cinmethylin and bensuhde prevent mitotic entry by unknown mechanisms (194). 

Bastenie and Zylberszac, in a general article on the former subject, point out that colchicine (1) brings into mitosis all cells which are in karyo-kinetic inuninence but which normally would slowly and successively reach mitosis, and (2) stops them at this stage. This has made possible a technique which picks out cell multiplication and can be used for detecting many types of hormonal stimulation, e.g., the action of follicular hormone and other oestrogens. ... 

When mitosis is blocked by colchicine, the treated cells may be left with an extra set of chromosomes. Plants with extra sets of chromosomes are typically larger and more vigorous than normal plants. Flowers developed in this way may grow with double the normal number of petals, and fruits may produce much larger amounts of sugar. 

Another drug is taxol, which is extracted from the bark of the Pacific yew tree, Taxus brevijolia. Unlike colchicine and the vinca alkaloids, taxol binds tightly to microtubules and stabilizes them against depolymerization by Ca. It also enhances the rate and yield of microtubule assembly, thereby decreasing the amount of soluble tubulin in the cytosol pool. Again, the overall effect of taxol is to arrest dividing cells in mitosis. Taxol is used in cancer chemotherapy. 

FIG. 2. Sister chromatid separation does not depend on the mitotic spindle. Light micrographs of mitosis in living flattened endosperm from Haemanthus katherinae BAK. treated with colchicine (c-mitosis). The micrographs were taken at 10 min intervals. Size bar, 10 /tm. Reprinted with permission from Mole-Bajer (1958). 

The chromatid separation process has also remained mysterious. It is an autonomous process that does not direcdy depend on the mitotic spindle (Wilson 1925, Mazia 1961). This is most vividly seen in cells whose spindles have been destroyed by spindle poisons such as colchicine. In many organisms, in particular in plant cells, the cell cycle delay induced by colchicine is only transient and chromatids eventually split apart in the complete absence of a mitotic spindle (Mole-Bajer 1958, Rieder Palazzo 1992) (Fig. 2). Mitosis in the presence of colchicine or colcemid (known as c-mitosis) leads to the production of daughter cells with twice the normal complement of chromosomes. This process is routinely used for manipulating plant genomes and may contribute to the therapeutic effects of taxol in treating breast cancer. 

Colchicine is allelochemical from Colchicium genera, which binds the tubulin and prevents the mitosis (Fig. 2) Cytochalasin B, cell permeable fungal toxin from Helminthosporium dematiodeum, which inhibits cell division by blocking the active polymerization and formation of contractile actomyosin microfilaments, inhibit the germination of microspores (Roshchina, 2005a). Therefore, one mechanism of action of some allelochemicals from plants and... 

I 14. The answer is a. (Hardman, pp 1259, 1260.) The vinca alkaloids, vincristine and vinblastine, have proved valuable because they work on a different principle from most cancer chemotherapeutic agents They (like colchicine) inhibit mitosis in metaphase by their ability to bind to tubulin. This prevents the formation of tubules and, consequently, the orderly arrangement of chromosomes, which apparently causes cell death. 

Colchicine (6) is used in the treatment of a broad range of diseases including acute gout and Mediterranean fever [28] and induces depolymerization of tubulin. This compound (6) distorts the tubulin/microtubule equilibrium by binding to the tubulin dimer and halting mitosis in the metaphase. The reason this approach is such a successful target in cancer therapy is that... 

Observations are made in metaphase cells arrested with a spindle inhibitor such as colchicine or colcemid to accumulate cells in a metaphase-like stage of mitosis (c-metaphase) before hypotonic treatment to enlarge cells and fixation with alcohol-acetic acid solution. Cells are then dispersed on to microscope slides and stained and slides are randomized, coded and analyzed for chromosome aberrations with high-power light microscopy. Details of the procedure are given in Dean and Danford (1984) and Preston et al. (1981, 1987). The UKEMS guidelines (Scott et al., 1990) recommend that all tests be repeated regardless of the outcome of the first test and... 

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. 

Mammalian cells in vitro are exposed to the test chemical with and without an exogenous mammalian metaboUc activation system and cultured for two rounds of replication in bromodeox3Uiridine (BrdU) containing medium. After treatment with a spindle inhibitor (e.g., colchicine) to accumulate cells in a metaphase-Uke stage of mitosis (c-metaphase), cells are harvested, stained, and metaphase cells analyzed for SCEs. Primary cultures (e.g., human lymphocytes) or established cell lines (e.g., Chinese hamster ovary or lung cells) may be used in the assay. At least three adequately spaced concentrations of the test substance should be used. 

Haggarty, S.J. Mayer, T.U. Miyamoto, D.T. Fathi, R. King, R.W. Mitchison, T.J. SchreibCT, S.L. (2000) Dissecting cellular processes using small molecules identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. Chem. Biol., 7, 275-86. 

Inhibition of spindle formation such as that caused by vincristine or colchicine stops separation of chromosomes at anaphase (see chap. 6). Proper separation of chromatids may not occur because of "stickiness 7 or bridging between the chromatids. Clearly, interference with mitosis, and hence cell proliferation, is an important cause of teratogenic effects. 

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. 

Ostergren, C. (1944) Colchicine mitosis chromosome contractions, narcosis and protein chain folding. Hereditas, 30, 429-467... 

Microtubules in cells undergoing mitosis are the target of several important drugs. One of these is the alkaloid colchicine which is produced by various members of the lily family and has been used since ancient Egyptian times for the alleviation of the symptoms of gout.a b... 

Colchicine can arrest plant and animal cell division in vitro and in vivo. Mitosis is arrested in metaphase because of failure of spindle formation. Cells with the highest rates of division are affected earliest. High concentrations may completely prevent cells from entering mitosis, and they often die. The action also is characteristic of the vinca alkaloids (vincristine and vinblastine), podophyllotoxin, and griseofulvin. 

Microtubule filaments are hollow cylinders made of the protein tubulin. The wall of the microtubule is made up of a helical array of alternating a- and 13-tubulin subunits. The mitotic spindle involved in separating the chromosomes during cell division is made of microtubules. Colchicine inhibits microtubule formation, whereas the anticancer agent, taxol, stabilizes microtubules and interferes with mitosis. 

The centrioles migrate to opposite poles of the cell and the mitotic spindle is formed, apparently joining the cell membrane through the centrioles to the centromere of each chromosome. Spindle fibres consist of one type of protein, tubulin, of molecular weight 60,000. It is the organisation of these molecules to form the mitotic spindle which is blocked by the drugs colchicine, colcemide, nocodazole, vincristine and vinblastine (Fig. 10.3) with the consequence that mitosis is arrested in metaphase. 

Cells in mitosis may be selectively removed and discarded over a long period of time. This leaves behind a population most of which should be in G2-phase (Stubblefield, 1964 Creasey and Markiw, 1965 Pfeiffer and Tolmach, 1967). Unfortunately, as well as the probability of selecting slow growers, the use of colchicine, colcemid and vinblastine may not only inhibit mitosis but may also have other effects on cells such as inhibition of RNA synthesis. 

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