Mitotic poisons

Liang JC, Hsu TC, Henry JE. 1983. Cytogenetic assays for mitotic poisons. The grasshopper embryo system for volatile liquids. Mutat Res 113 467-479. 

The best known drugs acting as antimitotics are the vinca alkaloids, vincristine (7.90) and vinblastine (7.91). They are very complex indole derivatives that nevertheless have been synthesized. Both are quite effective in various leukemias and in Hodgkin s lymphoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically to the microtubular protein tubulin in dimeric form, precipitating depolymerization of the microtubules and functionally acting as a mitotic poison. Vinorelbine (7.92) is a semisynthetic vinca alkaloid functionally identical to vinblastine. 

Mercier el al. (330) administered i.v. infusions of sodium salicylate to dogs and determined the lethal dose to be 1 g/kg. Simultaneous administration of papaverine resulted in a slight increase in the toxicity. Lettr6 et al. (331) studied the synergism of mitotic poisons and found that papaverine intensified the mitotic effect of colchicine on the growth of fibroblasts in vitro. The spasmolytic effect of khelline was augmented by small doses of papaverine (332). Therapeutic doses of khelline did not produce a hypotensive effect upon dogs, but in combination with barbiturates and papaverine a hypotensive effect was observed. 

Narcotine potentiates the effect of colchicine during inhibition of mitoses (619-622) narcotine itself is no mitotic poison. Administration... 

Summarising research results relevant to the activity and mode of action of this group of herbicides, Swanson (1972) concludes that, as with carbamates, the mode of action of dinitroaniline herbicides is the inhibition of mitosis. Dinitroaniline herbicides are thus mitotic poisons. 

Effects NSAIDs and glucocorticoids reduce the synthesis of mediators of inflammation by inflammatory cells in the gouty joint. Because it reacts with tubulin and interferes with microtubule assembly, colchicine is a general mitotic poison. Tubulin is necessary for normal cell division, motility, and many other processes. 

Types of Cell Division Effects. Classification of herbicidal effects on cell division is not uniform. This has lead to confusion about the action of herbicides on cell division. Terms such as "mitotic poisons", "meristem active", and "mitotic inhibitors" have been used to describe the same effect of a herbicide on cell division. A more useful classification of herbicidal effects would be to divide herbicides into 2 classes those inhibiting cell division and those disrupting cell division (Figure 1). Inhibition of cell division will result in treated meristems that only contain interphase cells. If cell division is disrupted, one or more mitotic stages normally present in the meristem tissue will not be found. These two effects on cell division result from different mechanisms. 

Some other substances, whose action is quite the contrary ofMCPA (methyl-chlorophenoxyacetic acid), can eliminate monocotyledonous weeds from a dicotyledon crop. For this purpose 2,2-dichloropropionic acid (dalapon, Dowpon ) is much used. Its mode of action is discussed in Section 9.4.1. The carbamates, which are mitotic poisons, introduced by Templeman and Sexton (1945), are also available for this purpose. The most selective example is barban (6.72) (4-chlorobut-2-ynyl AT,3 -chlorophenylcarbamate), which suppresses the... 

J.J, Biesele, Mitotic Poisons and the Cancer Problem (Elsevier, Amsterdam, 1958). 

Alkaloids are one of the most important groups of secondary metabolites used since prehistoric age. It has been used as an anti-inflammatory agent for a long time. Besides, as a potential mitotic poison, colchicine is applied to produce polyploid and double haploid plants by the plant breeders. Colchicine is... 

Colchicine has long been used as the potent chromosome-doubling agent. It induces chromosome doubling by inhibiting mitotic spindle of dividing cells. Mechanism of mitotic poisoning by colchicine has recently been elucidated. Colchicine has direct effect on microtubule assembly. 

TVowell OA 1960 The cytocidal action of mitotic poisons on lymphocytes in vitro. Biochem Pharmacol 5 53-63... 

Colchicine is a mitotic poison, in particular in thymic, intestinal and haematopoietic cells, and acts as a spindle poison and blocks the kinesis [2], Its effect on the mitotic spindle is thought to represent a special case of its effects on various organised, labile, fibrillar systems concerned with structure and movement [139, 140],... 

Woody nightshade. Solarium dulcamara, has been used from the time of Galen (c. AD 180) for the treatment of cancers. Recent studies on the plant have shown that the steroidal alkaloid glycoside -solamarine is active against S 180 [344] however, its low therapeutic index precludes it from further pharmacological study. A number of steroidal alkaloid glycosides have been reported to have cytostatic activity [345], and solananine to be a mitotic poison [346]. 

At the nonspecific level, the —SH group can be pictured to play an in vivo role in providing protection against ionizing rays, heavy metal and, mitotic poisons, or as in regulating the activity of metal-dependent enzymes, by its power to complex metals. 

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