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Biomedical subjects

J F Henderson

Publications and source records attributed to J F Henderson.

At least 37 records · Page 2Linked to original sources
PubMed1982

Relationship between ribo- and deoxyribonucleotide concentrations and biological parameters in cultured Chinese hamster ovary cells.

The relationship between ribo- and deoxyribonucleotide concentrations, growth rate and cell visibility has been studied. Nucleotide pools were manipulated using mycophenolic acid, pyrazofurin, phosphonoacetyl-L-aspartate (PALA) or thymidine. Growth rate, cell viability, nigrosin exclusion, progression through the cell cycle, and the rates of nucleic acid synthesis were measured. The observed qualitative relationships between nucleotide concentrations and growth rate can be rationalized in terms of the effects of changes in substrate availability on nucleic acid synthesis. However, there is no discernible relationship between changes in nucleotide concentrations and the loss of cell viability. More detailed studies will be required to elucidate each step in the complex process leading from the initial changes in nucleotide concentrations to cell death.

Amides↗
PubMed1982

Comparison of purine and pyrimidine metabolism in G1 and S phases of HeLa and Chinese hamster ovary cells.

Detailed quantitative studies of purine and pyrimidine metabolism in G1 and S phases of synchronized HeLa and Chinese hamster ovary cells have been carried out. Concentrations of ribonucleoside triphosphates increased approximately in proportion to the increase in cell size as cells moved from G1 to S phase. Deoxyribonucleoside triphosphate concentrations were low in G1 phase and increased 2.5- to 10-fold in S phase. Pathways and rates of metabolism of radioactive adenine, guanosine, deoxyadenosine, deoxyguanosine, uridine, cytidine, deoxyuridine, deoxycytidine, and thymidine were determined by measuring the incorporation of each precursor into individual acid-soluble nucleotides and RNA and DNA bases. Cell-cycle or size-dependent differences were detected in many of the parameters studied.

Adenine↗
PubMed1982

Models of the regulation of ribonucleotide reductase and their evaluation in intact mammalian cells.

Enzymological studies have shown that ribonucleotide reductase is allosterically inhibited or stimulated by endproduct deoxyribonucleoside triphosphates, and various investigators have put forward schematized models of the regulation of this enzyme; the various models have in practice been considered to be equivalent or at least very similar. Here each of eleven published models is critically examined, and it is shown that there are important differences among them that have not previously been appreciated. In addition, studies using intact mammalian cells have generally been taken as being consistent with the enzymological data, but this point has not received much systematic attention. The available data are examined critically, and the implications of multiple, partially different models are considered.

Animals↗
PubMed1981

Determination of deoxyribonucleoside triphosphates using DNA polymerase: a critical evaluation.

There are more than twenty appreciably different deoxyribonucleoside triphosphate assays using DNA polymerase in the literature. Therefore, each aspect of this method has been critically evaluated, including the purity of the substrates and of DNA polymerase, the reaction conditions, product isolation, and the effect of cell extracts on the assay. The final method uses a phosphatase-free DNA polymerase preparation, 2'-dAMP to inhibit the 3' leads to 5' exonuclease of DNA polymerase I, and includes a correction of both the background incorporation and the sample incorporation for dilution of the specific activity of the radioactive precursor by the sample. The sensitivity, range, accuracy, and reproducibility are reported as well as values for the deoxyribonucleoside triphosphate content of Chinese hamster ovary K-1 cells.

Animals↗
PubMed1981

Effects of altered ribonucleotide concentrations on ribonucleotide reduction in intact Chinese hamster ovary cells.

The effect of changes in ribonucleoside triphosphate concentrations on those of deoxyribonucleotides has been determined in Chinese hamster ovary K-1 cells. Ribonucleoside triphosphate concentrations were manipulated by the use of drugs or naturally occurring purines or pyrimidines. Changes in the concentration of each ribonucleoside triphosphate led to changes in the concentration of each corresponding deoxyribonucleoside triphosphate. The relationships between the concentrations of CTP and dCTP and between those of GTP and dGTP were linear over a wide range. The relationship between the concentrations of ATP and dATP was linear over the narrow range studied, while the relationship between UTP and dTTP concentrations was curvilinear. Overall, these results demonstrate that ribonucleotides play an important role in controlling deoxyribonucleotide concentrations but the exact mechanism of this control remains to be determined.

Animals↗
PubMed1981

Regulation of ribonucleotide reduction by deoxyribonucleotides in intact Chinese hamster ovary cells.

The ribonucleotide reductase model of Thelander and Reichard, which is based on studies of the purified enzyme, has been tested in cultured Chinese hamster ovary K-1 cells. Deoxyribonucleoside triphosphate concentrations were manipulated by the use of drugs or naturally occurring deoxyribonucleosides, and ribo- and deoxyribo-nucleoside triphosphate concentrations were measured. The results are consistent with the hypothesis that dTTP inhibits CDP reduction and stimulates GDP reduction, and that dGTP inhibits CDP reduction. However, the results are contrary to the hypothesis that dGTP inhibits UDP reduction and stimulates ADP reduction, and that dATP inhibits CDP reduction. It is concluded that the model of Thelander and Reichard applies only in part to intact CHO cells.

Animals↗
PubMed1981

Quantitative analysis of purine and pyrimidine metabolism in Chinese hamster ovary cells.

A detailed quantitative study of purine and pyrimidine metabolism in logarithmically growing Chinese hamster ovary cells has been performed. Direct measurements of the ribonucleoside and deoxyribonucleoside triphosphate pool sizes have been made, and the pathways and rates of metabolism of adenine, hypoxanthine, guanine, guanosine, deoxyadenosine, and deoxyguanosine and of uridine, cytidine, deoxycytidine, deoxyuridine, and thymidine have been determined.

Animals↗
PubMed1979

Relationships among purine nucleoside metabolism, adenosine triphosphate catabolism, and glycolysis in human erythrocytes.

In human erythrocytes incubated with both naturally occurring purine nucleosides and with a variety of purine nucleoside analogs, ATP catabolism was accelerated and lactate accumulation was increased. Tubercidin was a particularly potent inducer of ATP catabolism. In cells incubated with tubercidin, the major route of adenylate metabolism was deamination, whereas in cells incubated with deoxyglucose, the major pathway was dephosphorylation.

Adenosine Deaminase Inhibitors↗