scholarly journals STUDIES ON THE MECHANISM OF ACTION OF PEDERINE

1968 ◽  
Vol 36 (3) ◽  
pp. 485-496 ◽  
Author(s):  
Agnese Brega ◽  
Arturo Falaschi ◽  
Luigi De Carli ◽  
Mario Pavan
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Cytotoxic Effect ◽  
Rna Synthesis ◽  
Cultured Cells ◽  
Specific Inhibitor ◽  
Cytological Examination ◽  
Effect Analysis ◽  
Inhibitor Of Protein Synthesis

Pederine, a drug extracted from the coleopter Paederus fuscipes, inhibits the growth of in vitro cultured cell lines at concentrations of the order of 1.5 nanogram/ml. Cytological examination shows a generalized cytotoxic effect. Analysis of macromolecular syntheses by the use of radioactive precursors shows that pederine causes an almost immediate block of protein and DNA synthesis, without affecting RNA synthesis. The effects on the synthesis of the two types of macromolecules remain nearly simultaneous even at the lowest active concentrations of pederine. Studies with cell-free systems show that the drug inhibits protein synthesis, whereas it is ineffective on the DNA-polymerizing activity. It seems, therefore, that the drug acts primarily on the amino acid-polymerizing system, and that the effect on DNA is secondary. This idea is strengthened by the observation that puromycin, a specific inhibitor of protein synthesis, also affects promptly DNA synthesis of in vitro cultured cells. Other authors have shown the same phenomenon with a number of inhibitors of protein synthesis; the properties of pederine support, therefore, the view that continuous protein synthesis is necessary for the maintenance of DNA replication in higher organisms.

EFFECT OF X-IRRADIATION ON DNA SYNTHESIS IN EHRLICH ASCITES CARCINOMA CELLS

1965 ◽  
Vol 43 (7) ◽  
pp. 859-864 ◽  
Author(s):  
Shan-Ching Sung
Keyword(s):  
Protein Synthesis ◽  
Dna Synthesis ◽  
Rna Synthesis ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Total Rna ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells ◽  
X Irradiation

The rate of DNA synthesis in Ehrlich ascites cells measured immediately after X-irradiation of 500 r for 6 minutes in vitro showed about 15% reduction. However, if X-irradiation was followed by preincubation of the cells, the subsequent synthesis of DNA in the X-irradiated cells was markedly inhibited. Under the same condition, the uptake of thymidine-2-C14, uridine-2-C14, adenine-8-C14, and glycine-1-C14, and protein synthesis in the X-irradiated cells were found to be almost the same as those in the non-irradiated control. RNA synthesis measured as total RNA was only slightly inhibited.

scholarly journals STUDIES ON THE MECHANISM OF ENDOGENOUS PYROGEN PRODUCTION

1974 ◽  
Vol 140 (4) ◽  
pp. 954-964 ◽  
Author(s):  
Phyllis Bodel
Keyword(s):  
Protein Synthesis ◽  
Dose Response ◽  
Human Blood ◽  
Temperature Elevation ◽  
Blood Monocytes ◽  
Endogenous Pyrogen ◽  
Inhibitor Of Protein Synthesis ◽  
Relationship Of ◽  
Pyrogenic Activity

The characteristics of pyrogen production and release by human blood monocytes were investigated. A dose-response assay of monocyte pyrogen in rabbits indicated a linear relationship of temperature elevation to dose of pyrogen at lower doses. Monocytes did not contain pyrogen when first obtained, nor did they release it spontaneously even after 5 days of incubation in vitro. Pyrogen production was apparent 4 h after stimulation by endotoxin or phagocytosis, and continued for 24 h or more. Puromycin, an inhibitor of protein synthesis, prevented both initiation and continuation of pyrogen production and release. Pyrogen-containing supernates retained most pyrogenic activity during overnight incubation even in the presence of activated cells. Lymphocytes appeared to play no role in either initiation or continuation of pyrogen production in these studies.

The Effect of Insulin on the Growth and Metabolism of the Human Diploid Cell, Wi-38

1970 ◽  
Vol 7 (2) ◽  
pp. 575-585
Author(s):  
J. B. GRIFFITHS
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Glucose Uptake ◽  
Rna Synthesis ◽  
Cultured Cells ◽  
Cell Sheet ◽  
High Energy ◽  
Contact Inhibition ◽  
Contributory Factor ◽  
Membrane Area

In a confluent culture of WI-38 cells the membrane area available for nutrient uptake is greatly reduced and the possibility exists that this reduction in uptake capacity of the cell is a contributory factor in contact inhibition. Insulin has been reported by many authors to facilitate glucose uptake and also to stimulate protein, DNA and RNA synthesis, glycolysis, pino-cytosis and growth in cultured cells. The effect of insulin on WI-38 cells was determined, therefore, to find out whether it enabled the cell to escape from contact inhibition of growth. The action of insulin was found to be dependent upon medium composition. Growth and protein synthesis were stimulated in Eagle's minimal essential medium, but not when this medium was supplemented with glucose and glutamine. Apparently insulin is only effective when high-energy compounds become limiting. Whilst insulin did not induce any post-confluent division, the protein content of cells was increased by 30%, and this was correlated with an increased rate of protein synthesis. Despite this increased activity in protein metabolism, the utilization of amino acids was less in the presence of insulin indicating that a control mechanism for more economical utilization of amino acids for protein synthesis was activated by insulin. Insulin had no effect on RNA synthesis, and only a slight inhibitory effect on DNA synthesis. Evidence was produced suggesting that insulin blocked cell division and encouraged differentiation. Glucose uptake and incorporation into the cell was stimulated by insulin, and this was especially noticeable after the cell sheet became confluent. The turnover of labelled glucose and derivatives was also enhanced by insulin and this was accompanied by a much higher rate of lactic acid production. It is concluded that insulin does not overcome contact inhibition and permit post-confluent division, but that it does enable the cell to take up and utilize nutrients more efficiently in confluent cultures with a resultant increase in metabolic activity and cell size.

Effect of Daunorubicin and Adriamycin on Nucleic ACID Synthesis of Serum Stimulated Mouse Embryo Fibroblasts

1977 ◽  
Vol 63 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Rosanna Supino ◽  
Anna M. Casazza ◽  
Aurelio Di Marco
Keyword(s):  
Dna Synthesis ◽  
Mouse Embryo ◽  
Rna Synthesis ◽  
Calf Serum ◽  
Acid Synthesis ◽  
Anthracycline Antibiotics ◽  
Simple Method ◽  
Mouse Embryo Fibroblasts ◽  
Embryo Fibroblasts

This paper reports the effects of daunorubicin and adriamycin on DNA and RNA synthesis of in vitro cultured mouse embryo fibroblasts (MEF) stimulated by fetal calf serum (FCS). The addition of FCS to quiescent MEF cultures brings about a wave of RNA synthesis, followed by DNA synthesis which starts between 8 and 12 h after change of medium and proceed for up to 24 h. These cells are therefore partially synchronized. The level of DNA synthesis depends on the amount of FCS added. Daunorubicin and adriamycin are almost equally effective in inhibiting DNA synthesis, as well as cell proliferation, which takes place later. Adriamycin is more active than daunorubicin on RNA synthesis. In cultures treated for an 8 h period starting at different times after FCS addition, the highest DNA synthesis inhibition is achieved by treatment during the first 8 h, when DNA synthesis has not yet started. The cellular uptake of daunorubicin is constantly higher than that of adriamycin, in any experimental condition tested. The results show that FCS-stimulated MEF can provide a simple method for studying the effects of anthracycline antibiotics on partially synchronized cells.

scholarly journals LIMITED DNA SYNTHESIS IN THE ABSENCE OF PROTEIN SYNTHESIS IN PHYSARUM POLYCEPHALUM

1966 ◽  
Vol 31 (3) ◽  
pp. 577-583 ◽  
Author(s):  
J. E. Cummins ◽  
H. P. Rusch
Keyword(s):  
Protein Synthesis ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Physarum Polycephalum ◽  
Nuclear Dna ◽  
S Phase ◽  
Early Prophase ◽  
Late Prophase ◽  
Removal Experiments ◽  
Inhibitor Of Protein Synthesis

Actidione (cycloheximide), an antibiotic inhibitor of protein synthesis, blocked the incorporation of leucine and lysine during the S phase of Physarum polycephalum. Actidione added during the early prophase period in which mitosis is blocked totally inhibited the initiation of DNA synthesis. Actidione treatment in late prophase, which permitted mitosis in the absence of protein synthesis, permitted initiation of a round of DNA replication making up between 20 and 30% of the unreplicated nuclear DNA. Actidione treatment during the S phase permitted a round of replication similar to the effect at the beginning of S. The DNA synthesized in the presence of actidione was replicated semiconservatively and was stable through at least the mitosis following antibiotic removal. Experiments in which fluorodeoxyuridine inhibition was followed by thymidine reversal in the presence of actidione suggest that the early rounds of DNA replication must be completed before later rounds are initiated.

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