Effect of cell density on the inhibition of tumor cell attachment and nucleic acid synthesis by selenite

The effect of cell density on the sensitivity of tumor celles to selenite has been examined. The inhibitory effect of selenite on cellular DNA and RNA synthesis was significantly greater in higher density cultures of HeLa cells and A2780 ovarian tumor cells. High-density cells were also more sensitive to the inhibitory effect of selenite on cell attachment. This difference could not be accounted for by a higher intracellular level of glutathione, since there was no significant difference between the cells at high or low density. The high-density cells were found to take up more selenium per cell during the exposure period; the resulting higher level of intracellular Se could explain their greater sensitivity to selenite. This hypothesis is supported by the observation that DNA synthesis in nuclei isolated from high-density cells did not exhibit higher sensitivity to inhibition by selenite than synthesis in nuclei isolated from low-density cells.     

Influence of mitoxantrone on nucleic acid synthesis on the T-47D breast tumor cell line

Mitoxantrone exerts growth inhibitory effects, suppresses [3H]-thymidine as well as [3H]-uridine incorporation, and induces ultrastructural alterations in T-47D human breast tumor cells. At low concentration (10(-9)M) the drug induced little effect on cell proliferation; cell growth kinetics were inhibited at a concentration of 10(-5)M. [3H]-thymidine and [3H]-uridine incorporation declined rapidly at the concentrations tested (10(-9), 10(-7), and 10(-5) M), revealing a potent effect on metabolic activity of the cultured cells. The sharpest decline in DNA and RNA synthesis occurred within the first 2 hr of drug treatment. Serial ultrastructural examinations indicated definitive alterations in chromatin structure, disintegration of nucleolar components as early as 2 hr after drug treatment, and complete segregation of nucleolar components following 8-hr exposure to concentrations of the drug between 10(-5) and 10(-7) M. A distinct increase in the density of mitochrondrial matrix was evident. The in vitro data presented in this report demonstrate the growth inhibitory and antimetabolic effects of mitoxantrone on human breast tumor cells and suggest that the drug may be a promising antitumor agent.     

Effects of cell entrapment on nucleic acid content and microbial diversity of mixed cultures in biological wastewater treatment

The effects of entrapment on nucleic acid content and microbial diversity of mixed cultures in biological municipal wastewater treatment were investigated. Deoxyribonucleic acid content increased 1.6-5.5 times more in alginate entrapped cells than in free and polyvinyl alcohol (PVA) entrapped cells. PVA entrapment resulted in 1.1- to 5.9-fold more increases in ribonucleic acid content compared to that experienced by free and alginate entrapped cells. Entrapment in carrageenan changed the bacterial community structure more than the alginate and PVA entrapments (35-80% versus 0-35%) as determined by single-strand conformation polymorphism analyses. The change in the bacterial community structure of alginate entrapped cells was less time dependent than that of PVA entrapped cells. This study enhances understandings on the physiology of entrapped cells and their community evolution in wastewater treatment environments.     

Effect of thiopyrimidine ribonucleosides on DNA and RNA synthesis in synchronized mammalian cell cultures

The uptake of ³H-uridine into RNA and of ³H-thymidine into DNA was investigated in synchronized Chinese hamster cells which had been exposed to thiopyrimidine ribonucleosides. The cells were synchronized at metaphase by reversal of colcemid inhibition; these cells were then labeled with either ³H-thymidine or ³H-uridine at selected times, and analyzed in autoradiographs. Incorporation of ³H-thymidine into DNA was not inhibited by administration to the cells of 2-thiouridine or 4-thiouridine (4 × 10⁻³ M). Exposure of the cells to the anti-metabolites for over 15 h significantly reduced the incorporation of ³H-uridine into nuclear RNA and completely blocked the labeling of cytoplasmic RNA. This finding is interpreted as an indication that RNA synthesis was inhibited in cells which continued to synthesize DNA. The inhibition of RNA synthesis hindered cell division and decreased cell viability. This lethal effect is similar to the “unbalanced growth” induced by inhibitors of DNA synthesis. The thiopyrimidine ribonucleosides, however, killed mammalian cells without inhibiting DNA synthesis.     

Toxicity of para-aminobenzhydrazide and its influence on nucleic acid biosynthesis in cultures of normal and tumor cells

We have investigated cytotoxic action of p-aminobenzhydrazide and its influence on biosynthesis of nucleic acids in cultures of intact cells, tumor cells and intact cells stimulated by phytohemagglutinin. p-Aminobenzhydrazide is considered as a representative of hydrazine's derivatives (in particular, of hydrazine sulphate). We compare its action with that of a typical cytotoxic agent such as iododeoxyuridine. We have found that p-aminobenzhydrazide influences biosynthesis of nucleic acids in the same way as iododeoxyuridine. However it acts toxically on tumor cells though it is not toxic for intact cells so that its action is different as compared to that of cytotoxic agents. Specific toxic action of aminobenzhydrazide on tumor cells may be due to the enhancement of antitumor activity substances of this compound and absence of such enhancement of side toxic effects.     

Effects of macronutrients on growth and rosmarinic acid formation in cell suspension cultures of Anchusa officinalis

The influence of various macronutrients on growth and RA formation in cell suspension cultures of Anchusa officinalis has been investigated. Factors tested included sucrose concentration, alternate carbon sources, nitrate, phosphate and calcium concentration. The optimum concentration of sucrose was 3%. Fructose, glucose or their 1:1 mixture were also suitable carbon sources. The optimum concentrations of nitrate (15 mM), phosphate (3 mM) and calcium (0.25 mM) were, respectively, 3/5, 3x, and 1/4 those in normal B5 medium, when tested separately. These concentrations improved not only the yield of RA but also cell growth to a similar degree (10%–50%). Studies on the combined effects of these optimum macronutrient concentrations in B5 medium showed that RA production is inhibited by 2,4-D-containing revised medium but stimulated by NAA-containing revised medium.Abbreviations RA rosmarinic acid - 2,4-D 2,4-dichlorophenoxyacetic acid - NAA 1-napthaleneacetic acid     

Inhibition of nucleic acid synthesis in Ehrlich tumor cells by periodate-oxidized adenosine and adenylic acid

Periodate-oxidized adenosine and AMP were inhibitory to both RNA and DNA synthesis in Ehrlich tumor cells in culture. With periodate-oxidized adenosine, the inhibition of RNA synthesis paralleled the inhibition of DNA synthesis. Periodate-oxidized AMP, however, was more inhibitory to DNA synthesis than to RNA synthesis. With both compounds, there was a decrease in the conversion of [¹⁴C]cytidine nucleotides to [¹⁴C]deoxycytidine nucleotides in the acid-soluble pool. The borohy-dride-reduced trialcohol derivative of the periodate-oxidized adenosine compound was not inhibitory to DNA or RNA synthesis in the tumor cells. The incorporation of [³H]uridine into 28S and 18S ribosomal RNA was inhibited by both periodate-oxidized adenosine and AMP, but the incorporation of [³H]uridine in 45S, 5S, and 4S RNA was essentially unaffected by these compounds. Periodate-oxidized adenosine inhibited Ehrlich tumor cell growth in vivo.