DNA synthesis, inhibition

Eukaryotic organisms HeLa cells DNA synthesis inhibition - - Painter and Howard 1982 KCN... 

Only one in vivo study was located. No testicular DNA-synthesis inhibition was detected in mice after a single oral dose of 1 mg/kg cyanide as potassium cyanide (Friedman and Staub 1976). The results indicate that cyanide, especially in a form of salts, is not mutagenic. 

Painter RB, Howard R. 1982. The HeLa DNA-synthesis inhibition test as a rapid screen for mutagenic carcinogens. Mutat Res 92 427-437. 

Illudin S (199) Sesquiter- penoid Irofulven (MGI-114, HMAF) (200) Oncology DNA synthesis inhibition Phase II/III (advanced-stage PC and advanced GI solid tumors) Eisai (MGI Pharma) 923-926... 

DNA synthesis inhibition. Ethanol (90%) extract of the dried entire plant at a concentration of 0.25 mg/mL, was active " " ". Fibrinolytic activity. Ether extracts of the dried gum and gum resin, administered orally to 10 healthy subjects fed 100 g of butter to produce alimentary hyperlipemia, were active " "". ... 

DNA synthesis inhibition. Leaves, on agar plate at a concentration of 50%, produced weak activity on monkey kidney cells . Smoke of the dried leaf, administered to rats at variable doses, produced weak activity " ". 

DNA synthesis inhibition. Ethanol (90%) extract of the dried entire plant, at a concentration of 0.25 mg/mL, was active . Early antigen viral induction stimulation. 

Binds to specific sites necessary Immortalizes and transforms for DNA synthesis inhibition of ... 

The observation of DNA synthesis inhibition, by measuring the radiolabeled precursor uptake in Ehrlich ascites and human AV3 cells46,47), whereas RNA and protein synthesis were hardly affected (see Fig. 8 for a summary). 

Gemcitabine is phosphorylated initially by the enzyme deoxycytidine kinase and then by other nucleoside kinases to the di- and triphosphate nucleotide forms, which then inhibit DNA synthesis. Inhibition is considered to result from two actions inhibition of ribonucleotide reductase by gemcitabine diphosphate, which reduces the level of deoxyribonucleoside triphosphates required for the synthesis of DNA and incorporation of gemcitabine triphosphate into DNA. Following incorporation of gemcitabine nucleotide, only one additional nucleotide can be added to the growing DNA strand, resulting in chain termination. 

Cao W, Mohacsi B Shorthouse R, Pratt R, Morris RE. Effects of rapamycin on growth factor-stimulated vascular smooth muscle cell DNA synthesis, Inhibition of basic fibroblast growth factor and platelet-derived growth factor action and antagonism of rapamycin by FK506, Transplantation 1995 3 390-395. 

The findings that demonstrated the activity of compound 4 (Fig. 9) under anaerobic conditions opened the studies of QDO as specific anti-microorganism agents. Anaerobic antibacterial mechanism of compound 4 involves DNA synthesis inhibition without effects on the RNA and proteins syntheses [114]. It has been demonstrated that compound 6 inhibits Staphylococcus aureus DNase biosynthesis and plasma coagulase [115]. 

Rabbit (bone marrow) DNA synthesis inhibition + Kissling and Speck 1972... 

Mouse (bone marrow cell culture) DNA synthesis inhibition No data + Lee et al. 1988... 

Human (HeLa cells) DNA synthesis inhibition — — Painter and Howard 1982... 

Small lymphocytes from horses were transformed into larger radioresistant lymphoblast-hke cells following stimulation by phytohemagglutinin in vitro. One hundred rads x-irradiation killed all the small lymphocytes, but only around one-third of the lymphoblast-like cells (Dewey and Brannon, 1976). Horse lymphocytes were more radiosensitive than human lymphocytes. The ratios between doses inducing the same effect are 1.3,1.7, and 9.4 for the number of binucleated cells with micronuclei, micronucleus frequency in binucleated cells, and DNA synthesis inhibition, respectively (Catena et al, 1997). 

Fluorouracil and relative drugs, metabolism, mechanism of RNA and DNA synthesis inhibition, pharmacology of 87PHA73. 

Takada Y, Kageyama K, Yamada R, et al. Correlation of DNA synthesis-inhibiting activity and the extent of transmembrane permeation into tumor cells by unsaturated or saturated fatty alcohols of graded chain-length upon hyperthermia. Oncol Rep 2001 8 547-551. 

Holotoxin Ai inhibits the RNA biosynthesis in Candida albicans and Saccharomyces carlsbergensis, as indicated by the decrease in incorporation of C-uridine to the acid-insoluble fraction of the cells. Similar results were obtained for glycoside fractions of 14 species of Pacific sea cucumbers [132]. Apparently the inhibition of RNA biosynthesis in Saccharomyces carlsbergensis is related to nucleotide loss from yeast cells after treatment with glycosides. Holotoxin Ai also inhibits biosyntheses of squalene, lanosterol and ergosterol in S. carlsbergensis [133]. Mitosis is arrested and DNA synthesis inhibited in onion root bulbs by crude holothurin [134]. 

Blocks conversion to dTMP by thymidylate synthetase, DNA synthesis inhibited... 

Toxic to testes in animals and humans Depression of libido and potency Replacement of phosphorus in DNA synthesis Inhibition of prostaglandins in seminal fluid Radiomimetic Azoospermia... 

Seiler JP. 1981. Testicular DNA synthesis inhibition an in vivo system for the detection of mutagenic and carcinogenic chemicals. Toxicol Environ Chem 3 239-249. 

Inhibits ribonucleotide reductase via inhibition of DNA synthesis inhibits DNA polymerase via inhibition of DNA repair... 

FH4 is carried out by the crucial enzyme thimidylate synthetase (Fig. 4-13). It should be noted that this is a reductive methylation where the tetrahydrofolate coenzyme serves both as a one-carbon donor and reductant. The resultant FH2 must be reduced back to FH4 by folate reductase, thus offering further opportunity for DNA synthesis inhibition at this point. Thymidylate synthetase is the sole de novo path to thymidylate there are no alternate routes. The interest of this point as a target for anticancer agents is obvious. 

Etoposide is a podophyllotoxin derivative. Its main effect appears to be at the G2 portion of the cell cycle. At high concentrations (10 mcg/mL or more), lysis of cells entering mitosis is seen at low concentrations (0.3 to 10 meg/ mL), cells are inhibited from entering prophase. Predominant macromolecular effect appears to be DNA synthesis inhibition. Etoposide is indicated in refractory testicular tumors, and smaU-ceU lung cancer. 

All eukaryotic ribonucleotide reductases assayed so far in vitro are inhibited by hydroxyurea, and a wide variety of eukaryotic cells and organisms is found susceptible to DNA synthesis inhibition by the drug . Nevertheless, a clearcut dependency like in E. coli cannot be stated as investigation of the eukaryotic enzymes is lagging and because hydroxyurea exerts manifold cellular effects, some without obvious relation to the inhibition of ribonucleotide reduction (cf. Table 9). 

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