Effects Of Antimitotic Agents Research Articles

Water diffusion in cytoplasmic streaming in Elodea internodal cells under the effect of antimitotic agents

The translational displacement of the cytoplasmic water in Elodea stem cells resulting from protein motor activity was measured using the NMR method. A 24-h treatment with vincristine results in a reduction of the translational displacement of the cytoplasmic water. With a constant cytoplasmic streaming velocity, the dynamics of the translational displacement of the cytoplasmic water under the effect of taxol are characterized by a continuous increase at a concentration of 0.05 mM, and reaching a plateau at a concentration of 0.5 mM.

Effect of anti-mitotic agents on development and genome doubling of gynogenic onion ( Allium cepa L.) embryos

The experiment was carried out in attempt to develop an efficient and simple protocol for diploidization of gynogenic onion ( Allium cepa L.) embryos. Well-developed embryos derived from flower bud cultures of different onion materials were used. Doubling took place in vitro, on two regeneration media supplemented with one of four anti-mitotic agents, i.e. trifluralin, oryzalin, amiprophos-methyl (APM) or colchicine in various concentrations. Embryos were plated on the media for 24 or 72 h and then transferred onto regeneration media without anti-microtubule compounds. Frequency of developing embryos ranged from 45 to 77% and was similar for both time regimes. In most combinations doubling substances caused some vitrification of developing embryos, on average 11%. Among the evaluated regenerants 19–35% were diploids. The highest doubling efficiency was achieved for embryos cultured on media supplemented with 50 μM trifluralin or oryzalin or APM. Since APM induced the least vitrification of the onion tissue it may be proposed as the best chromosome doubling compound for Allium cepa.

Effects of Antimitotic Agents on Haploid Plant Production from Unpollinated Ovules of Sugar Beet (Beta Vulgaris L.)

ABSTRACTThe effects of antimicrotubule agents on haploid embryo formation from unpollinated ovules of sugar beet (Beta vulgaris L.) were investigated. The antimitotic agent colchicine (at 100 and 150 mg/l) and trifluralin (at 5.0 mg/l) increased the frequency of haploid embryo formation whereas pronamide (at 76.9 and 128.2 mg/l) and trifluralin (at 3.4 mg/l) decreased. Ovules that were non-treated with antimicrotuble agents (i.e., ovules of the control treatment) produced higher percentages of haploid embryos (4.25%) when compared to the pronamide and trifluralin at 3.4 mg/l concentration. Toxic effects of these agents on embryo formation from ovules were evident. A significant genotypic variation among the lines used was observed. The line M4 produced the highest yield with a mean of 14.71% haploid embryo production while the line M2 producing no embryos at all.

Effects of antimitotic agents on secretion and detergent extractibility of adrenal nicotinic acetylcholine receptors.

1. Evidence exists that associations of adrenal nicotinic acetylcholine receptors (nAChRs) with the cytoskeleton play an important role in signal transduction pathways by maintaining these receptors in a functional state. These studies were designed to explore this possibility and elucidate the mechanism by which antimitotic agents inhibit activation of adrenal nAChRs. 2. Functional studies demonstrated that vincristine, tubulozole, podophyllotoxin, and demecolcine inhibited nAChR-stimulated catecholamine release noncompetitively and in a concentration-dependent manner, with IC50 values of 3 (1-10), 5 (2-10), 8 (4-15), and 19 (9-39) microM, respectively. 3. Detergent extraction experiments indicated that approximately 36% of adrenal nAChRs were associated with the detergent-insoluble cytoskeletal fraction. When chromaffin cells were first treated with antimitotic agents and then detergent solubilized, a significant reduction occurred in the population of adrenal nAChRs associated with the detergent-insoluble cytoskeleton. 4. These studies support an association of adrenal nAChRs with microtubules and suggest that the mechanism by which the antimitotic drugs interfere with the signal transduction pathway is by inducing dissociation of nAChRs from the microtubular network.

The effect of antimitotic agents on the intraneuronal distribution of lysosomes

We previously showed that a single injection of colchicine into the lateral cerebral ventricle of the rat causes a redistribution of lysosomes from their normal localization in neuronal cell bodies into dendrites. In the present report we have examined the time course and specificity of this effect using a variety of microtubule poisons. Dipeptidylaminopeptidase II (Dpp II), a lysosomal marker enzyme, histochemistry was used to visualize lysosomes at the light microscopic level. Acid phosphatase, another lysosomal enzyme, histochemistry was used to confirm the Dpp II localization of lysosomes. Two h after an intracerebroventricular (i.c.v.) injection of colchicine, the distribution of neuronal lysosomes was drastically altered. Lysosomes in a number of neuronal populations were observed to move from the soma to the dendrites. This effect was maximal between 12 and 24 h and was partially reversed by 96 h. Injections of colcemid or podophyllotoxin, drugs that bind to tubulin rapidly, and much less tightly than colchicine, produced a much less pronounced alteration in the intraneuronal distribution of lysosomes. Injections of vinblastine or vincristine, whose binding kinetics range between that of chochicine and that of colcemid and podophyllotoxin, resulted in a redistribution of lysosomes which was less pronounced than the effects of colchicine but more pronounced than that caused by colcemid and podophyllotoxin. Likewise, treatment with other related compounds, 2-methoxy-5-(2′,3′,4′-trimethoxyphenyl) tropone (A-C compound) and lumicolchicine, whose binding to tubulin is extremely rapid and reversible or non-existent, produced little or no alteration in the intraneuronal distribution of lysosomes. The results suggest that lysosome redistribution may be dependent upon a relatively slow dissociation rate constant of these drugs from tubulin, and this transport may occur when normal microtubule function is compromised.

Effects of antimitotic agents either free or bound to DNA on mouse peritoneal macrophages cultivated in vitro

Mouse peritoneal macrophages were cultivated in vitro and treated with ethidium bromide (EB) or with cis-dichloro-diammine platinum (II) (cis-Pt). EB provokes strong cytological alterations and cell degeneration; cis-Pt was not toxic under our experimental contitions. EB-DNA complex penetrates into the macrophages, is liberated from DNA in vacuoles, then diffuses into the cell and is highly cytotoxic. Cis-Pt-DNA complex also penetrates into the cells, but cis-Pt cannot be released from DNA, cis-Pt-DNA complex accumulates inside cytoplasmic vacuoles but has no cytotoxic activity.

Differential effects of inhibitors of cell division upon the growth stimulating activities of insulin and serum in nutritionally depleted human and mouse cells.

Cultured mouse and human cells were arrested in their growth by artificially depriving them of phosphate. The quiescent cells could be stimulated to synthesize DNA and to divide by addition to the growth medium of insulin, dialyzed serum and/or the full concentration of phosphate. In order to gain insight into mechanisms by which insulin and serum stimulate growth, the inhibitory effects of antimitotic agents were examined. Of the inhibitors tested, vinblastine and cytocalasin B abolished the growth promoting activity of insulin, while colchicine inhibited the activity of both serum and insulin. The present results suggest that insulin-stimulated growth is meciated by a different path way than serum-stimulated growth and is sensitive to mechanisms that occur at various times prior to insulin addition.

The aggregation of rabbit polymorphonuclear leucocytes: effects of antimitotic agents, cyclic nucleotides and methyl xanthines.

ABSTRACT The aggregation of rabbit peritoneal exudate polymorphonuclear leucocytes (PMNs) was investigated by following total particle number with time, in a shaken suspension. Aggregation was rapid and essentially complete by 30 min, but could be inhibited by microtubule-blocking agents, adenosine and methyl xanthines. The addition of cyclic adenosine 3’:s’-mono-phosphate (cAMP), or its dibutyryl derivative, also inhibited aggregation slightly, but guanosine nucleotides had no significant effect. By consideration of the maximum inhibition brought about by colchicine or theophylline alone, or the two in combination, it appears that they act at different sites to inhibit aggregation, though the effects of either were partially reversed by the addition of adenine. Adenine, lumicolchicine and high concentrations of vinblastine sulphate (10−4 M), enhanced aggregation.

Effects of antimitotic agents on Ehrlich ascites cells

The biochemical effects on Ehrlich ascites cells of acriflavine, podophyllotoxin, 6-hydroxylaminopurine, and 8-ethoxycaffeine, compounds known to inhibit cell multiplication, were studied. Acriflavine was shown to inhibit DNA synthesis, and extracts of cells preincubated with acriflavine were less able to synthesize inosinate. Podophyllotoxin was a potent inliibitor of purine synthesis in vitro but relatively ineffective in vivo. It did block purine interconversion, and the general inhibitory effects of the agent were attributed to this action. The adenine analog, 6-hydroxylaminopurine, blocked the conversion of inosinate to adenylate and guanylate. This specific inhibition led to a generalized decrease in formation of nucleic acids. Purine synthesis de novo was blocked by 8-ethoxycaffeine in extracts of ascites cells, the effect was much greater when the cells had been preincubated with the inhibitor. The action of this compound was attributed to this specific block. The compounds each appeared to have distinct modes of action. It is suggested that some of these may mimic natural mechanisms of control of cell division.