Synergistic effect of purine derivatives on the toxicity of pyrazofurin and 6-azauridine towards cultured mammalian cells

A novel synergistic effect of several purine derivatives such as adenine, adenosine, hypoxanthine, and guanine on the toxicity of nucleoside analogs pyrazofurin and 6-azauridine towards cultured Chinese hamster ovary (CHO) cells has been observed. The presence of the above purine derivatives enhanced the toxicity of pyrazofurin and 6-azauridine, in a dose dependent manner. The growth inhibitory effects of these nucleoside analogs either alone or in combination with the purine derivatives were reversed by uridine and cytidine, providing evidence that the synergistic effect of the purine derivatives was exerted at the level of pyrimidine nucleotide biosynthesis. Studies with mutant cells lacking various purine phosphorylating enzymes show that phosphorylation of purine derivatives through reactions utilizing phosphoribosylpyrophosate (PRPP) is essential for observing the synergistic response. It is suggested that the above purine derivatives (including adenosine, via conversion to hypoxanthine) exert their synergistic effects by depleting the cellular pool of PRPP by two separate mechanisms (direct utilization and feedback inhibition of its synthesis), which as a result becomes rate limiting in the synthesis of orotidine monophosphate (OMP). The reduced levels of OMP, which is a competing substrate with pyrazofurin- and 6-azauridine-5'-monophosphates for binding to the target enzyme OMP decarboxylase, could then account for the inhibition of the enzyme at lower concentrations of these analogs.     

Species specific differences in the toxicity of mithramycin, chromomycin A3, and olivomycin towards cultured mammalian cells

Three structurally related anticancer drugs, mithramycin, chromomycin A3, and olivomycin, showed large unexpected differences (up to more than 1000 fold) in their toxicity towards cultured cells from various species (human, Chinese hamster, Syrian hamster, and mouse). Among the cell types examined, human cells (both a diploid fibroblast cell strain and HeLa cells) were maximally sensitive to all these drugs, followed by the Syrian hamster kidney cells (BHK 21). The mouse (LMTK- cells) and Chinese hamster (CHO) cells, which were more resistant, showed interesting differences in their sensitivity towards these drugs. For example, whereas the mouse cells were more resistant to mithramycin than CHO cells, the sensitivity pattern was reversed for both chromomycin A3 and olivomycin. In cell extracts derived from human, mouse, and Chinese hamster cells RNA synthesis, which is the cellular target of these drugs, showed identical sensitivity to both mithramycin and chromomycin A3, indicating that the species specific differences in the toxicity to these drugs are at the level of cellular entry of these compounds. Based on the structures of these glycosidic antibiotics and their patterns of toxicity, it is suggested that the intracellular transport of these drugs involves specific interactions between the sugar residues on these compounds and some type of cell surface receptor(s), which differ among different cell types. Some implications of these results for toxicity studies are discussed.     

Genesis of microspore-derived triploid petunias

Summary A total of 61 microspore-derived plants of Petunia parodii were grown to maturity revealing a predominent population of triploids, 80.3%. Cytological investigations, together with the evidence from microfluorimetry, suggest that the origin of these triploids was due to the fusion of interphase nuclei in two different pathways. In the majority of embryogenic microspores, a vegetative nucleus of 1C DNA content fused with an endo-reduplicated 2C DNA generative nucleus at the binucleate stage and produced true triploid embryoids and plantlets (A pathway). Where this fusion failed, both the vegetative and the generative nuclei divided separately and in the multinucleate microspore two or more daughter nuclei fused to form a mixoploid embryoid. Such mixoploid embryoids produced a mixed population of plants with various ploidy levels as well as ploidy polymorphism within an individual. Since the triploids are morphologically superior with a faster growth rate than their diploids and related tetraploids, a predominent population of triploid plants was obtained from such mixoploid embryoids (B pathway). By low temperature treatment of the anther-donor buds, the embryogenic response of microspores was enhanced up to 5-fold.     

Microprobe analysis of Na,K, Cl,P, S,Ca, Mg and H2O in frozen-hydrated sections of anterior caeca of the locust, Schistocerca gregaria

Electron probe X-ray microanalysis of frozen-hydrated sections was carried out for sodium, potassium, chlorine, calcium, magnesium, sulphur, phosphorus and water concentrations in the lumen and epithelial cells of freshly-fed adult female desert locusts, and in blood of fed and starved locusts.Sodium and chloride were found to be at a much lower level in the lumen and cells than potassium, and at a much higher level in the blood. The luminal folds were plugged with a dense organic matrix, presumed to be polyanionic glycosaminoglycans, which appeared to restrict access of charged moieties of the absorptive sites. The data were consistent with a model of caecal fluid absorption in which a passive flux of potassium from lumen to blood, possibly assisted by an active absorption of chloride, drives fluid into the blood. Unlike the case of the vertebrate intestine, active absorption of sodium from the lumen would not contribute significantly to the fluid transport in vivo.     

Improvements in optical methods for measuring rapid changes in membrane potential

Summary In an effort to increase the utility of optical methods for measuring membrane potential in excitable cells, an additional 369 dyes were tested on giant axons from the squid. Several promising dyes with relatively large absorption and fluorescence signals are described. In addition, a simple modification of the apparatus led to a sixfold increase in the size of dye-related birefringence signals. In preparations with a suitable geometry, these signals are as large as absorption signals but photodynamic damage and bleaching are eliminated when wavelengths longer than the absorption band are used.     

Hirsutinolides from Vernonia species

Out of the nineteen species of Vernonia studied, five contained highly oxygenated sesquiterpene lactones, while the rest contained predominantly triterpenes, especially lupane derivatives.     

Steroid hormone effects on growth and apical dominance of sunflower

External application of estradiol-17β increased shoot growth but decreased root growth of sunflower seedlings. It completely inhibited cotyledonary axillary bud development in decapitated plants at the concentration of 1 μg/plant. Concentrations lower than this promoted cotyledonary axillary bud formation. Testosterone on the other hand inhibited both shoot and root growth and promoted cotyledonary axillary bud formation at all the concentrations used. Progesterone at high (0.25,μg/plant) concentration promoted shoot growth but inhibited root growth. A low concentration (0.1 μg/plant) of progesterone produced the opposite effect.