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At least 19 recordsLinked to original sources
PubMed1975

Uptake in vitro of nucleic acid precursors and nucleic acids by Zajdela ascitic hepatoma cells.

Zajdela ascitic hepatoma cells are shown to take up pyrimidine bases at much lower rates than obtained in slices from normal rat liver. The rates of uptake of adenine and uridine by the Zajdela cells are, however, as high as in the slices. Like the slices, again, the Zajdela cells take up E. coli RNA and DNA at very low rates but, unlike the slices, thses cells degrade rapidly the RNA taken up. The Zajdela cells resemble parenchymal cell suspensions derived from normal rat liver in regard to the uptake of pyrimidine bases and the ability to degrade heterologous RNA.

Adenine↗
PubMed1996

Antagonistic effect of nucleic acid precursors on the anticoccidial activity of 6-azauracil.

The antagonistic phenomena to anticoccidial activities of 6-azauracil (AzU) induced by certain nucleic acid precursors were examined in battery experiments. Each nucleic acid precursor, orotate, orotidine, uracil, uridine, adenine and adenosine was mixed in feed in combination with effective levels of AzU. The test feed was provided through the test term to White Leghorn cockerels which were infected with Eimeria tenella, E. necatrix or E. acervulina. In vitro tests were also conducted for antagonistic phenomena similarly to in vivo test using E. tenella cultured in chick kidney (CK) cells. Orotate and uridine reduced dose-dependently the anticoccidial activity of AzU in E. tenella infection in chickens. Uracil and orotidine revealed similar effect. Adenine and adenosine did not show any antagonistic effect to AzU. In E. necatrix infection, orotate and uridine had a similar tendency to that of E. tenella, whereas uracil and orotidine was less pronounced. The activity of AzU against E. acervulina was also blocked by the treatment with uridine and orotate. AzU inhibited the schizont's development of E. tenella in the CK cells, and this effect was reduced by uridine, but not by orotate and orotidine. The antagonistic effect of the pyrimidine nucleic acid precursors on AzU activity suggested that the anticoccidial effect of AzU to E. tenella, E. necatrix and E. acervulina is derived from inhibition of the metabolism of pyrimidine nucleotide synthesis in these parasites.

Adenine↗
PubMed1984

Enhancement of the sensitivity of human colon cancer cells to growth inhibition by acivicin achieved through inhibition of nucleic acid precursor salvage by dipyridamole.

This study was undertaken to determine if salvage of nucleic acid precursors might constitute a mechanism of resistance to acivicin in human colon cancer cells and, if so, to establish whether dipyridamole, an inhibitor of nucleoside and nucleobase transport, can block the salvage process and restore sensitivity to acivicin. Acivicin inhibited the replication of human colon cancer cells (VACO 5) in vitro in a dose- and time-dependent fashion. In addition, marked cell lysis was evident after a 24-hr exposure to acivicin at concentrations greater than 1 microgram/ml. The primary metabolic effect of acivicin was depletion of the cytidine triphosphate and guanosine triphosphate pools. Adenosine triphosphate levels were also reduced, but apparently as a consequence of the guanosine triphosphate depletion. VACO 5 cells exposed to acivicin (3 micrograms/ml) efficiently salvaged low levels (1 micron) of cytidine, guanosine, and guanine and could, therefore, restore the depleted nucleotide pools. The combination of cytidine and guanosine, but not either nucleoside alone, provided significant protection against the growth-inhibitory properties of acivicin. Dipyridamole, at a noncytotoxic concentration (5 microM), blocked repletion of the cytidine triphosphate and guanosine triphosphate pools in cells exposed to acivicin and the nucleic acid precursors. As a result, the growth-inhibitory effects of acivicin were maintained. The salvage of cytidine was particularly sensitive to inhibition by dipyridamole, and no restoration of cytidine triphosphate pools was evident. The cellular uptake of a variety of nucleic acid precursors was differentially sensitive to inhibition by dipyridamole. The 50% inhibitory dose values ranged from 0.01 to 2.5 microM for cytidine and uridine, respectively. The results of this study indicate that, although the replication of VACO 5 cells was inhibited by acivicin, low levels of nucleosides and nucleobases can circumvent the cytotoxicity. Dipyridamole effectively blocked the salvage pathways and restored the sensitivity of the cancer cells to the antiproliferative actions of acivicin.

Antibiotics, Antineoplastic↗
PubMed1990

[Basic study on the chemosensitivity test by miniaturized improved nucleic acid precursor incorporation assay (MINI assay)].

UNLABELLED: Miniaturized improved nucleic acid precursor incorporation assay (MINI assay) has been developed by Kern D. H. and Tanigawa N. et al since 1985. We investigated in vitro effects of mitomycin C (MMC), cisplatin (CDDP) and bleomycin (BLM) against A 549 lung cancer cells and HeLa cells by MINI assay. RESULTS: 3H-thymidine (3H-TdR) uptake in the positive control was 734.2 cpm +/- 10 cpm. The cut-off level for in vitro sensitivity was defined as more than 80% inhibition of 3H-TdR uptake in the drug treated cells compared to the positive controls. A 549 cells were sensitive to MMC (81.6%), CDDP (78.6%), but not to BLM (-57%). HeLa cells were sensitive to MMC (91%), CDDP (79.4%), but not to BLM (43%). MINI assay could be done with fewer cells than other methods and the results were obtained within 5 days. This method was considered to be useful for the chemosensitivity test with human tumors.

Antineoplastic Agents↗
PubMed1974

In vitro antimalarial activity of nucleic acid precursor analogues in the simian malaria Plasmodium knowlesi.

Analogues of nucleic acid precursors were screened for antimalarial activity in Plasmodium knowlesi by using an in vitro culture system. Activity was assessed by the degree of inhibition of incorporation of l-[methyl-(14)C]methionine into protein and of [8-(14)C]adenosine and [6-(14)C]orotic acid into ribonucleic acid and deoxyribonucleic acid. The incorporation of adenosine or orotic acid was effectively inhibited by many of the compounds, including 3' analogues of purine nucleosides, many of the 6-position analogues of purine bases and nucleosides, and 5-position analogues of orotic acid. Only a few compounds inhibited methionine incorporation into protein, and in each instance adenosine or orotic acid incorporation also was inhibited. Some compounds inhibited adenosine or orotic acid incorporation into both ribonucleic acid and deoxyribonucleic, whereas other analogues inhibited incorporation into one nucleic acid only. The qualitative and quantitative differences suggest that this experimental system may be appropriate for investigation of metabolic pathways of the malaria parasite, as well as for demonstration of antimalarial activity of candidate antimalaria drugs.

Animals↗
PubMedDate not supplied

[Characteristics of the levels of various nucleic acid precursors in the tissues of rabbits with various thyroid conditions].

The content of the precursors and metabolites of nucleic acids in the brain and liver of normal rabbits, rabbits with hypothyrosis (thyroidectomy) and hyperthyrosis (100-150 Mg of L-thyroxine per 1 kg of body mass daily for 10-12 days) was determined by liquid chromatography with a high resolution. A decrease in the content of deoxyguanosine, thymine, hypoxanthine, cytosine, thymidine and an increase in the content of inosine, adenine and adenosine in the liver of animals with hypothyrosis were shown. In the brain of these rabbits the level of cytidine was lowered, and the levels of deoxyguanosine, thymine, inosine, hypoxanthine, adenine and uracil were on an increase. An increase in the levels of deoxyguanosine, thymine, adenine, thymidine and a decrease in the levels of cytidine, hypoxanthine, cytosine, adenine and uracil in the liver were noted in hyperthyrosis. In the brain of rabbits with hyperthyrosis an increase in the levels of deoxyguanosine, cytidine, inosine and adenine was combined with a decrease in the levels of thymine and hypoxanthine. These thyroid-dependent changes in the content of registered metabolites and precursors of nucleic acids in tissues suggest that the observed shifts illustrate one of many mechanisms of the regulation of cell metabolism by thyroid hormones.

Adenine↗
PubMed1979

Incorporation studies of nucleic acid precursors in gastric cancer: an attempt in individualized chemotherapy.

Measurements of the rate of incorporation of radioactively labeled nucleic acid precursors into the DNA and RNA of gastric carcinoma cell suspensions indicated variable rates of proliferation for the tumors. The rate of incorporation generally correlates to the cytological level of differentiation of the carcinoma. Reduced differentiation of the tumors showed a corresponding increase in the rate of proliferation. Knowing the proliferation-dependent effect of most cytostatica, this results in a resistance to cytostatica of highly differentiated gastric cancers. The nucleic acid synthesis of proliferatively active tumors could only be partially inhibited by the cytostatica tested (5-fluorouracil, adriamycin). Carcinomas with metabolic possibility for compensation of the active mechanism of the cytostatica were biochemically resistant. Due to the resulting methodical problems and unaccountable patient-dependent causes of resistance, a conclusive statement about cytostatica-sensitive tumors is difficult to make in incorporation studies.

Antineoplastic Agents↗
PubMed1982

Selected nucleic Acid precursors in studies of aquatic microbial ecology.

The use of radiolabeled nucleosides and nucleic acid bases to estimate the rates of RNA and DNA synthesis in naturally occurring microbial assemblages requires numerous assumptions, several of which are evaluated herein. Comparative time series analyses of the uptake and incorporation, labeling specificity, and extent of catabolism of [2-H]adenine, [methyl-H]thymidine, and [5-H]uridine were performed with pure bacterial and algal cultures, as well as with environmental samples. [H]thymidine yielded the most variable results, especially with regard to the extent of nonspecific macromolecular labeling. The pathways of [H]thymidine and [H]adenine metabolism were further evaluated by isotope dilution methods and by comparing incorporation patterns of thymidine labeled at different sites of the molecule. The advantages, uncertainties, and limitations of the use of radiolabeled nucleic acid precursors in studies of aquatic microbial ecology are discussed and a prospectus for future studies presented.

Journal Article↗
PubMed1977

[On the problem of praetherapeutic sensitivity testing of human tumours based on incorporation studies of nucleic acid precursors in vitro (author's transl)].

Praetherapeutic sensitivity tests of human solid tumours based on incorporation studies of nucleic acid precursors have been described by various authors. This review intends to show that such tests may only be of rather limited value for the design of individual chemotherapeutic regimens. In many drugs, a correlation between biochemical and clinical effects has not yet been established. The reliability of praetherapeutic sensitivity tests is further impaired by general methodological difficulties of short-term cultures, individual pharmacology and toxicology of cytostatic agents as well as pharmacological and biochemical drug interactions in combination chemotherapy. Praetherapeutic testing with individual cytostatic drugs is discussed.

Alkylating Agents↗
PubMed1969

Stimulation of incorporation of nucleic acid precursors into HeLa cells caused by proflavine.

1. The effect of proflavine and other acridines on the incorporation of precursors into the nucleic acids of HeLa cells was examined. 2. Relatively low concentrations (50mum) of proflavine completely inhibited incorporation of precursors into DNA, but allowed a small extent of incorporation into RNA. 3. Acridine-resistant incorporation into RNA was unaffected by actinomycin D at 2mug./ml. and persisted even at high concentrations (500mum) of many acridines. 4. A few combinations of acridine and precursor, notably 250mum-proflavine and [(14)C]adenine, caused a stimulation of incorporation. 5. The proflavine-stimulated incorporation was into alkali-stable di- and tri-nucleotides. 6. It was concluded that the effect was due to the preferential inhibition of degradation of a fraction of RNA that normally turned over, thus allowing small radioactive oligonucleotides to accumulate in the cells.

Acridines↗
PubMed1975

Incorporation of nucleic acid precursors by Plasmodium cynomolgi in Anopheles balabacensis.

Autoradiography was used to study the incorporation of tritium-labelled nucleic acid precursors into the sporogonic stages of Plasmodium cynomolgi in Anopheles b. balabacensis. Infected mosquitoes were fed on either 3H-adenine (5, 25 and 50 muCi/ml or 3H-thymidine (50 muCi/ml) for various periods after the blood meal. 3H-adenine was incorporated into DNA and RNA of the developing oocysts and the resulting sporozoites. Midgut epithelial cells incorporated label from 3H-adenine into nuclear and cytoplasmic regions. In both parasite and host tissue RNA-label was removed after RNase treatment. 3H-thymidine was not taken up by the developing oocysts or sporozoites while incorporation into the cell nuclei of the adjacent midgut epithelium and fat-body of the mosquito was shown. The observed incorporation of 3H-adenine, but not 3H-thymidine, into the sporogonic stages of Plasmodium supports the assumption that the malaria parasite needs exogenous sources of purine but relies on the de novo synthesis of pyrimidine during its development in the mosquito.

Adenine↗
PubMed2001

Competence development by Haemophilus influenzae is regulated by the availability of nucleic acid precursors.

DNA uptake by naturally competent bacteria provides cells with both genetic information and nucleotides. In Haemophilus influenzae, competence development requires both cAMP and an unidentified signal arising under starvation conditions. To investigate this signal, competence induction was examined in media supplemented with nucleic acid precursors. The addition of physiological levels of AMP and GMP reduced competence 200-fold and prevented the normal competence-induced transcription of the essential competence genes comA and rec-2. The rich medium normally used for growth allows only limited competence. Capillary electrophoresis revealed only a subinhibitory amount of AMP and no detectable GMP, and the addition of AMP or GMP to this medium also reduced competence 20- to 100-fold. Neither a functional stringent response system nor a functional phosphoenolpyruvate:glycose phosphotransferase system (PTS) was found to be required for purine-mediated repression. Added cAMP partially restored both transcription of competence genes and competence development, suggesting that purines may reduce the response to cAMP. Potential binding sites for the PurR repressor were identified in several competence genes, suggesting that competence is part of the PUR regulon. These observations are consistent with models of competence regulation, in which depleted purine pools signal the need for nucleotides, and support the hypothesis that competence evolved primarily for nucleotide acquisition.

Adenosine Monophosphate↗
PubMed1985

Development of a miniaturized, improved nucleic acid precursor incorporation assay for chemosensitivity testing of human solid tumors.

Two technological problems limit the usefulness of chemosensitivity assays: low success rates (generally 30-60%); and the requirement for large numbers of tumor cells (5 X 10(5)/dish). To solve these problems, we developed a miniaturized, improved, nucleic acid precursor incorporation assay (MINI-assay). In this new assay, 0.3-1.5 X 10(5) tumor cells were plated in double-layer agarose in 16-mm wells of a Costar (No. 3524) 24-well cluster dish. After 72 h of incubation, 5 microCi [3H]thymidine were added to each well. After an additional 24 h of incubation, the trichloroacetic acid-precipitable material was collected and counted by liquid scintillation. We found that 280 of 351 (80%) human solid tumors gave evaluable chemosensitivity results. Labeling efficiency was optimum when the plating density was between 1.5 and 3 X 10(4) cells/well. Radioisotope uptake was less efficient in 35-mm Petri dishes and in the 7-mm wells. The MINI-assay was particularly suitable for small specimens (less than 1 g) and for tumor types that usually yield small numbers of viable tumor cells (19 of 30 breast cancers and 56 of 71 sarcomas were evaluable). The artifacts of colony counting (cell clumps, debris, clots) were also eliminated with this assay. With high evaluability rates, the requirement of fewer cells, a short duration (5 days), and ease of quantitation, the MINI-assay is widely applicable to chemosensitivity testing in human tumors.

Agar↗