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Journal of Cellular Physiology Dec 1992Pretreatment plus concomitant treatment with 10 micrograms/ml cycloheximide protected Chinese hamster ovary cells and Swiss 3T3 cells against the cytotoxicity of...
Pretreatment plus concomitant treatment with 10 micrograms/ml cycloheximide protected Chinese hamster ovary cells and Swiss 3T3 cells against the cytotoxicity of actinomycin D. The cycloheximide treatment reduced the intracellular concentration of actinomycin D by reducing the level of actinomycin D bound to the acid precipitable fraction of the cell. Levels of unbound actinomycin D were unaffected by cycloheximide, indicating that the plasma membrane permeability to AD was not reduced. Actinomycin D inhibited total transcription but did not reduce cytoplasmic levels of rRNA nor of most tested mRNA; however, cytoplasmic levels of c-myc mRNA were reduced below detectability. Cycloheximide treatment further inhibited total transcription and had no effect on cytoplasmic levels of rRNA nor of most tested mRNA. Cytoplasmic levels of c-myc were elevated by cycloheximide and remained so even in the presence of actinomycin D. These data suggested that a reduction in cytoplasmic levels of short lived, essential mRNA, such as c-myc mRNA, was one lethal lesion of actinomycin D. Furthermore, cycloheximide's protection may result, in part, from its ability to stabilize and/or elevate cytoplasmic levels of these mRNA, thus counteracting their depletion by actinomycin D. Protection may also result from the cycloheximide-induced reduction of actinomycin D bound to the acid precipitable fraction of the cells.
Topics: Animals; Blotting, Northern; CHO Cells; Cell Line; Cell Survival; Cricetinae; Cycloheximide; Dactinomycin; Intracellular Membranes; RNA; Temperature; Uridine
PubMed: 1280278
DOI: 10.1002/jcp.1041530310 -
Antibiotiki Dec 1969
Topics: Bacillus; Bacillus subtilis; Bacteria; Candida; Dactinomycin; Depression, Chemical; Drug Resistance, Microbial; Hydrogen-Ion Concentration; Immunodiffusion; Methods; Microbial Sensitivity Tests; Sarcina; Staphylococcus
PubMed: 4190062
DOI: No ID Found -
The Journal of Antibiotics Apr 2013Streptomyces chrysomallus and Streptomyces parvulus produce novel C-demethylactinomycins besides their normal actinomycins when fed with 3-hydroxyanthranilic acid...
Streptomyces chrysomallus and Streptomyces parvulus produce novel C-demethylactinomycins besides their normal actinomycins when fed with 3-hydroxyanthranilic acid (3-HA). The 3-HA is incorporated into pentapeptide lactone precursors in competition with the regular precursor 4-methyl-3-hydroxyanthranilic acid (4-MHA). The resultant 3-HA pentapeptide lactones can condense with each other, as well as with the continuously formed 4-MHA pentapeptide lactones giving C-demethylactinomycins lacking one or both methyl groups in their phenoxazinone chromophores. In case of C-demethylactinomyins lacking one methyl group, the condensation was shown to be regiospecific directing the 3-HA portion almost exclusively to the α-side of the phenoxazinone chromophore. As 3-HA is a weaker substrate for the 4-MHA-incorporating enzyme actinomycin synthetase I than 4-MHA, C-demethylactinomycins never exceeded 7-8% of total actinomycin formed. Surprisingly, C-demethylactinomycins (up to 0.8%) were also found in the actinomycin mixtures of unsupplemented streptomycete cultures after longer cultivation times, indicating the natural presence of 3-HA. Feeding with 3-hydroxykynurenine (3-HK) induced also formation of C-demethylactinomycins indicating that 3-HK is source of 3-HA. Analysis of tryptophan metabolites in the intracellular pools of the streptomycetes using 5-(3)H-tryptophan as radiotracer revealed formation of 4-MHA, but not of 3-HA. This indicates that intracellular 3-HK is almost exclusively converted to 3-hydroxy-4-methylkynurenine (4-MHK), which has been identified previously as direct precursor of 4-MHA. However, small amount of 3-HK leaking out from the 4-MHA pathway can be prematurely converted to 3-HA all along the cultivation of the streptomycetes resulting in the formation of natural C-demethylactinomycins.
Topics: 3-Hydroxyanthranilic Acid; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Dactinomycin; Mycelium; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptomyces
PubMed: 23423168
DOI: 10.1038/ja.2012.120 -
Annals of the New York Academy of... Oct 1960
Topics: Dactinomycin; Humans
PubMed: 13735270
DOI: 10.1111/j.1749-6632.1960.tb20158.x -
Natural Product Research Jan 2019Actinomycin Z (1), a new member of the actinomycin family, along with three congeners of the Z-type (Z, Z, Z) actinomycins, are produced from Streptomyces sp. KIB-H714....
Actinomycin Z (1), a new member of the actinomycin family, along with three congeners of the Z-type (Z, Z, Z) actinomycins, are produced from Streptomyces sp. KIB-H714. Their structures were authenticated by comprehensive spectroscopic data interpretation. Different from all the reported Z-type actinomycins, the β-ring of the new compound actinomycin Z includes an additional ring linked between the actinoyl chromophore and β-peptidolactone. In Z and Z, the L-threonine in β-depsipeptide is replaced by the unusual 4-chlorothreonine, an amino acid rarely found in actinomycin family. All isolates were evaluated for cytotoxicity against five human tumor cell lines and for inhibitory activity against Candida albicans and Staphylococcus aureus.
Topics: Anti-Infective Agents; Antineoplastic Agents; Candida albicans; Cell Line, Tumor; Dactinomycin; Drug Evaluation, Preclinical; Humans; Magnetic Resonance Spectroscopy; Molecular Structure; Oxygen; Spectrometry, Mass, Electrospray Ionization; Staphylococcus aureus; Streptomyces; Structure-Activity Relationship; Threonine
PubMed: 29495881
DOI: 10.1080/14786419.2018.1443097 -
Antimicrobial Agents and Chemotherapy Feb 1976Streptomyces antibioticus synthesizes five actinomycins that differ in the "proline site" of the molecule. When cultured in the presence of azetidine-2-carboxylic acid...
Streptomyces antibioticus synthesizes five actinomycins that differ in the "proline site" of the molecule. When cultured in the presence of azetidine-2-carboxylic acid (AzC), antibiotic synthesis was stimulated 40 to 50%, synthesis of actinomycin IV was inhibited, and one or both prolines were replaced by AzC. AzC incorporation could not be reversed by concomitant supplementation with proline or sarcosine, and only pipecolic acid affected a minor reversal of AzC incorporation. AzC-containing actinomycins were isolated and designated azet-I and azet-II; a third unresolved component or mixture was called azet-III. The molar ratio of AzC to proline was: azet-I, 1:1; azet-II, 2:0. Azet-III was equivocal. These azetidine actinomycins (azetomycins) were found to be potently inhibitory to the growth of selected gram-positive but not as potent to the growth of gram-negative organisms. The relative inhibitory affect against growth and ribonucleic acid synthesis in Bacillus subtilis was: actinomycin IV =/> azet-I > azet-II >>> azet-III. Protein synthesis was affected similarly; however, kinetic studies with B. subtilis revealed that ribonucleic acid synthesis was inhibited rapidly followed by an inhibition of protein synthesis. At concentrations less than 1 mug/ml, deoxyribonucleic acid synthesis was stimulated by these actinomycins.
Topics: Amino Acids; Azetidinecarboxylic Acid; Bacillus subtilis; Bacterial Proteins; DNA, Bacterial; Dactinomycin; Drug Stability; RNA, Bacterial; Streptomyces; Streptomyces antibioticus; Time Factors
PubMed: 57738
DOI: 10.1128/AAC.9.2.214 -
Archives of Pharmacal Research Dec 1994An actinomycin complex isolated from culture broth of a soil microorganism, SNUS 9305011 has been examined by High performance liquid chromatography (HPLC). From the...
An actinomycin complex isolated from culture broth of a soil microorganism, SNUS 9305011 has been examined by High performance liquid chromatography (HPLC). From the analysis of the fractions obtained by column chromatography of the ethyl acetate extract, three actinomycin components are confirmed. The HPLC analysis is carried out with a CN-bonded nucleosil column. Comparison of the retention times of the components with those of actinomycin D, C complex X0 beta, and V suggests that they are different actinomycins. FAB mass spectra of the components also shows different molecular ions from those of standards and other reported actinomycins. The present work was has demonstrated that actinomycin components can be separated by a CN-bonded HPLC column, and that comparison of their HPLC chromatograms with authentic samples and information on their molecular ions can be successfully employed for identification of actinomycins.
Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Colony Count, Microbial; Dactinomycin; Mycobacterium; Spectrometry, Mass, Fast Atom Bombardment
PubMed: 10319152
DOI: 10.1007/BF02979119 -
The Journal of Pediatrics Feb 1972
Topics: Dactinomycin; Death, Sudden; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Postoperative Complications; Pulmonary Atelectasis
PubMed: 5008837
DOI: 10.1016/s0022-3476(72)80610-3 -
Pharmacology, Biochemistry, and Behavior May 1976The influence of Actinomycin D (AMD) applied intrahippocampally at doses of 1-6 mug/animal, on the acquisition and retention of a shock-motivated brightness...
The influence of Actinomycin D (AMD) applied intrahippocampally at doses of 1-6 mug/animal, on the acquisition and retention of a shock-motivated brightness discrimination was studied on rats in a semiautomatic Y-maze. The injection of AMD 4 hr prior to training did not influence the acquisition, but causes, dose-dependent, a retention loss in relearning 24 hr after training. Twenty-eight hr after AMD application, naive rats exhibited a deterioration of acquisition performance increasing equally with the dose. At the same time, both circumscribed necroses in the hippocampus and signs of a general intoxication were observed. Considering the described pro- and retroactive effects, it is concluded that the use of the inhibitor AMD in learning experiments is not suitable to provide reliable evidence of the specific importance of the cerebral RNA synthesis for memory consolidation.
Topics: Animals; Body Temperature; Body Weight; Dactinomycin; Hippocampus; Injections; Injections, Intraventricular; Learning; Male; Memory; Rats; Time Factors
PubMed: 951429
DOI: 10.1016/0091-3057(76)90190-8 -
Medical and Pediatric Oncology Feb 2001
Topics: Antibiotics, Antineoplastic; Child, Preschool; Dactinomycin; Female; Humans; Injections, Spinal; Lymphoma, T-Cell; Spinal Cord
PubMed: 11452950
DOI: 10.1002/1096-911X(20010201)36:2<339::AID-MPO1082>3.0.CO;2-Q