Cell division, effect

Some growth factors may be classified as cytokines (e.g. interleukins, TGF-P and CSFs). Others (e.g. IGFs) are not members of this family. Each growth factor has a mitogenic (promotes cell division) effect on a characteristic range of cells. Whereas some such factors affect only a few cell types, most stimulate growth of a wide range of cells. 

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. 

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. 

The growth inhibitory mechanism of the thiocarbamate herbicides, eg, EPTC, butylate, cycloate, diaHate, and triaHate, is not well defined. Cell elongation, rather than cell division, appears to be inhibited (183), although mitotic entry may be inhibited by diaHate (184). Thiocarbamates have a greater effect on shoot than toot tissue (163,184). The weU-documented inhibition of Hpid synthesis by thiocarbamates certainly contributes to the observed inhibitions of cell division and elongation. These compounds may also inhibit gibbereUic acid synthesis (185). 

In view of the well-documented inhibition of dihydrofolate reductase by aminopterin (325), methotrexate (326) and related compounds it is generally accepted that this inhibitory effect constitutes the primary metabolic action of folate analogues and results in a block in the conversion of folate and dihydrofolate (DHF) to THF and its derivatives. As a consequence of this block, tissues become deficient in the THF derivatives, and this deficiency has many consequences similar to those resulting from nutritional folate deficiency. The crucial effect, however, is a depression of thymidylate synthesis with a consequent failure in DNA synthesis and arrest of cell division that has lethal results in rapidly proliferating tissues such as intestinal mucosa and bone marrow (B-69MI21604, B-69MI21605). 

In addition to effects on biochemical reactions, the inhibitors may influence the permeability of the various cellular membranes and through physical and chemical effects may alter the structure of other subcellular structures such as proteins, nucleic acid, and spindle fibers. Unfortunately, few definite examples can be listed. The action of colchicine and podophyllin in interfering with cell division is well known. The effect of various lactones (coumarin, parasorbic acid, and protoanemonin) on mitotic activity was discussed above. Disturbances to cytoplasmic and vacuolar structure, and the morphology of mitochondria imposed by protoanemonin, were also mentioned. Interference with protein configuration and loss of biological activity was attributed to incorporation of azetidine-2-carboxylic acid into mung bean protein in place of proline. 

Tubulin is a major component of the cellular cytoskele-ton. Tubulin polymers (microtubules) are important for cell division (mitotic spindle) and the chemotaxis and phagocytosis of neutrophils. Prevention of tubulin polymerisation by colchicine accounts for the therapeutic effects of this drug in acute gouty arthritis and its anti-mitotic effects. 

Role of the Cytoskeleton in Cell Division Formation of the Mitotic Spindle, Mitosis, and Cytokinesis Drug Effects on Microtubules Mlcrofllaments Actin Filaments Structure and Composition... 

Several groups of drugs that bind to tubulin at different sites interfere with its polymerization into microtubules. These drugs are of experimental and clinical importance (Bershadsky and Vasiliev, 1988). For example, colchicine, an alkaloid derived from the meadow saffron plant Colchicum autumnale or Colchicum speciosum), is the oldest and most widely studied of these drugs. It forms a molecular complex with tubulin in the cytosol pool and prevents its polymerization into microtubules. Other substances such as colcemid, podophyllotoxin, and noco-dazole bind to the tubulin molecule at the same site as colchicine and produce a similar effect, albeit with some kinetic differences. Mature ciliary microtubules are resistant to colchicine, whereas those of the mitotic spindle are very sensitive. Colchicine and colcemid block cell division in metaphase and are widely used in cytogenetic studies of cultured cells to enhance the yield of metaphase plate chromosomes. 

The mode of action of starch capped copper nanoparticles (SCuNPs) was compared with that of the well-known antibiotic amphicillin (Fig. 9). There was a drastic decrease in the optical density of compounds containing SCuNPs and ampicillin, ultimately reaching almost zero suggesting that there were no more bacteria present in the culture. AmpiciUin at a concentration of 100 pg/ml has the ability to lyse E.coli almost immediately [29]. The same effect was produced by SCuNPs at 365 ng/ml concentration. The cell lysis occurs at the expense of the fact that at the point of cell division there occurs a deformation of the cell envelope. The decrease in optical density is possibly associated with the cell-envelope deformation occurring at the point of cell division [30]. 

Many in vitro studies have been undertaken to explore the relative effectiveness of isothiocyanates, and associated compounds, as inhibitors of cell growth and inducers of apoptosis in cell lines, and some of these are summarised in Table 4.2. Clonal survival studies are often used to determine whether isothiocyanates inhibit initial cell anchorage and subsequent growth of sparsely seeded cells. However, differences in cell number following challenge with the isothiocyanate could be due either to decreased cell division or increased cell loss, and the authors of some in vitro studies have failed to recognise this. Other studies have, however, considered the interacting... 

Table 4.2 Summary of smdies comparing the anti-proliferative effects against tumour cell lines of glucosinolate metabolites in vitro. The comparisons do not distinguish between increased cell death and reduced rate of cell division...

Temple S, Raff MC 1986 Clonal analysis of oligodendrocyte development in culture evidence for a developmental clock that counts cell divisions. Cell 44 773-779 Walters SN, Morell P 1981 Effects of altered thyroid states on myelinogenesis. J Neurochem 36 1792-1801... 

The effect of platinum in a bacterial cell is to act in a very selective way — on cell division or causing lysis of lysogenic bacteria. It is likely that these changes are due to site specific attack on particular proteins or on particular bases in RNA or in DNA. It is necessary now to describe this attack in detail and to develop new probes for following the site in vivo. This exercise can be followed by a parallel examination of how cis- [Pt (NH3) 2CI2] acts as an anti-tumour agent. Here we only point to some interesting observations. 

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