Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACTINOMYCIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1994

Cell cycle phase-dependent cytotoxicity of actinomycin D in HeLa cells.

The effects of brief actinomycin D treatment (0.1 microgram/ml, 0.5 h) on inhibition of cell growth and colony formation were studied in synchronized HeLa cells. Cells in late S and G2 phases were found to be maximally sensitive to inhibition of cell growth and colony formation after short exposure to actinomycin D. Cells in G1 and early S phases were less responsive to brief actinomycin D treatment, although there was a slowdown of cell growth between 24 and 48 h after removal of actinomycin D, recovery of cell growth was observed late (> 48 h) after drug removal. Cells in mitosis were maximally resistant to brief actinomycin D treatment, and continued to grow as did the control cells without drug. The effects of actinomycin D on inhibition of cell growth and colony formation were abolished by novobiocin but not by aphidicolin present during a brief actinomycin D treatment of cells at various cell cycle stages. Our results suggest that the effect of actinomycin D is cell cycle phase-dependent and may be involved in the action of topoisomerase II. Furthermore, actinomycin D at a low dose (0.1 microgram/ml, 0.5 h) induced a slight G1 block while a brief exposure to high dose actinomycin D (1.0 microgram/ml, 0.5 h) caused a slowdown in the rate of cell progression through S and G2/M phases. Similar S and G2/M phase block was seen in cells that had been briefly treated with actinomycin D (0.1 microgram/ml; 0.5 h) during late S and G2 phases.

Aphidicolin↗
PubMed1975

[Actinomycin DO inhibition of RNA biosynthesis and its interaction with DNA preparations].

Actinomycin D0 differing from actinomycin D in replacement of I residue of sarcosine by glycine in one of the peptide chains was found to have a lower inhibitory effect on RNA synthesis in various biological systems. On interaction of E. coli with DNA actinomycin D0 formed a complex with DNA having the binding constant K=1.6 with 10-5 which was 100 times lower than the binding constant of actinomycin D. Therefore, actinomycin D0 formed a complex with DNA which was 100 times less stable than actinomycin D. Actinomycins D0, D and II having different conformations in buffer on interaction with DNA formed complexes having similar conformations. The conformational change from free actinomycin to bound actinomycin was found difficult in case of actinomycin D0 because of its slow rate of complex formation with DNA as compared to that of other actinomycins complex formation with DNA.

Animals↗
PubMed1985

Natural cytotoxicity of human blood monocytes and natural killer cells and their cytotoxic factors: discriminating effects of actinomycin D.

The effect of actinomycin D on target susceptibility to human blood natural killer (NK) cells and monocytes was analysed in direct cell-mediated and their cytotoxic factor-mediated cytotoxicity assays. Treatment of K562 cells with actinomycin D reduced their susceptibility to lysis by non-adherent lymphocytes and Percoll-purified large granular lymphocytes (LGL) in a 4-hr 51Cr-release assay, without affecting their sensitivity to monocytes purified by adherence to autologous serum-coated plastic surfaces. The drug treatment caused no shift in the kinetics of cytotoxicity. In the target binding assay LGL formed fewer conjugates with actinomycin-D-treated K562 cells than with untreated ones, while the binding of monocytes to targets was not reduced by the drug treatment of K562 cells. The cold target competition assay revealed that actinomycin-D-treated cold K562 cells showed less successful inhibition than untreated cold K562 cells. Lymphocytes and monocytes could be induced to release soluble cytotoxic factors, termed natural killer cytotoxic factors (NKCF) and monocyte cytotoxic factors (MCF), respectively, when co-cultured with K562 cells. Both cytotoxic factors lysed NK-sensitive target cells in a 48-hr assay. Actinomycin-D-treated K562 cells reduced or abolished the ability to stimulate the release of NKCF from lymphocytes, whereas they induced MCF secretion from monocytes as effectively as untreated ones. On the other hand, actinomycin D treatment of K562 cells enhanced their susceptibility to NKCF and MCF. This actinomycin-D-induced augmentation of target sensitivity to the cytotoxic factors was restricted to NK-sensitive target cells (K562 and Molt-4). NK-resistant target cells (Raji, YAC-I, EL4 and T blasts) were not lysed by NKCF and MCF even after they were treated with actinomycin D. The capacity of K562 cells to bind NKCF and MCF was not altered by actinomycin D. Treatment of the adherent cell population with OKMI or Leu-MI plus complement abrogated both cell-mediated cytotoxicity and MCF production, while Leu-IIb plus complement was ineffective. These results suggest that the effect of actinomycin-D treatment can be used to distinguish the two distinct types of blood mononuclear cells with natural cytotoxicity, NK cells and monocytes, and that each effector type recognizes different plasma membrane moieties of NK target cells, although the cytotoxic factors released from each effector cell similarly bind to and lyse the target cells.

Animals↗
PubMed1993

Influence of DNA base sequence on the binding energetics of actinomycin D.

The influences of base sequence on the thermodynamic properties associated with the interaction of actinomycin D with DNA are examined. It has been previously established that GpC steps of double-helical DNAs are highly preferred binding sites for actinomycin D. In this study, a series of oligonucleotides was designed and synthesized to probe the effects of flanking base sequence (adjacent to the GpC step) and novel non-GpC binding sites on the binding of actinomycin D. The use of these oligonucleotides provides a direct method for quantitating sequence specificities and actinomycin D binding energetics. Effects of different 5' and 3' flanking nucleotides on the interactions of actinomycin with the core GpC binding sites were examined using UV-visible spectrophotometric methods, and changes in binding energetics were quantitated. These studies demonstrate strong actinomycin D binding affinities to both classical GpC and an atypical non-GpC site. Enthalpy and entropy components of the DNA binding energetics for the GpC binding sites are compared and correlated with those determined for actinomycin D binding to the high-affinity non-GpC site of an 11-mer containing TGGGT as the central sequence. This TGGGT site, first suggested to be a high-affinity sequence in our earlier photoaffinity labeling studies, exhibits binding of actinomycin D comparable in strength to that of traditional actinomycin D binding sites (i.e., GpC steps). From these studies, the overall affinity and specific thermodynamic contributions (delta H degree, delta S degree) to binding of actinomycin D are demonstrated to be highly influenced both by the sequence at the intercalation site and by neighboring bases which flank the intercalation site.

Amino Acid Sequence↗
PubMed1966

Effects of actinomycin D on nucleic acid metabolism and protein biosynthesis during metamorphosis of Tenebrio molitor L.

1. Injection of 0.16mug. of actinomycin D into pupae of the beetle Tenebrio molitor L. results in the development of modified adults in which the head and thorax are essentially adult while the abdomen and wings remain pupal-like. It is suggested that the messenger RNA for the development of head and thorax is present in the animal from the first day of pupation. 2. Injection of 0.16mug. of actinomycin D brings about 51-67% inhibition of labelled uridine incorporation into RNA. 3. When thymus DNA is mixed with actinomycin D before injection into pupae the latter develop into normal adults. This protection does not occur when DNA and actinomycin D are injected separately. 4. The inhibition of incorporation of labelled uridine into RNA by actinomycin is diminished to some extent when DNA and actinomycin D are injected separately and abolished if they are injected together. 5. Inhibition of RNA synthesis by actinomycin D in vitro is fully reversible. DNA or deoxyguanosine can reverse the effect of actinomycin D. 6. Incorporation of labelled glycine into protein is not affected by actinomycin D injection during the first 6 days of pupation. On the seventh day it becomes diminished in control pupae but this effect is prevented by actinomycin D. It is suggested that the template for protein synthesis is stable during the first 6 days of metamorphosis and that on the seventh day there is a qualitative change in the protein synthesized on the template.

Animals↗
PubMed1978

Induction of murine erythroleukemia differentiation by actinomycin D.

Murine erythroleukemia cells are induced to differentiate by 0.5-5 ng of actinomycin D per ml. Murine erythroleukemia cells cultured with actinomycin D prolong cell doubling time but achieve the same density after 5 days as cells without inducer. Actinomycin D causes over 95% of the cells to become benzidine-reactive. [(3)H]Actinomycin D uptake into DNA can be detected within 2 hr and reaches a maximum (approximately 0.1 pmol/10(6) cells) by 10-12 hr. It is estimated that about one out of 10(5) dG.dC pairs is bound to actinomycin D. Commitment to differentiation, assayed by transfer of cells to culture without inducer, was detected as early as 5 hr. Unlike Me(2)SO, which causes a transient prolongation in G(1) at about 15-20 hr, cells cultured with actinomycin D show a more sustained increase in the proportion of the cells in G(1). Globin mRNA accumulation was detectable by 19 hr in culture. Alteration in DNA stability in alkaline sucrose gradients was detected by 19 hr. Actinomycin D induces synthesis of Hb(maj) and Hb(min) in approximately equal amounts. A decrease in rates of synthesis of RNA, DNA, and total protein occurs in cells cultured with actinomycin D, as well as in cells cultured with Me(2)SO. No evidence for an early action of actinomycin D at the plasma membrane was obtained by measurement of changes in cell volume or (86)RbCl uptake. Taken together, the present results indicate that actinomycin D is a potent inducer of differentiation of murine erythroleukemia cells and suggest that the target of its effect may be at the level of DNA.

Animals↗
PubMed1988

Genetics of actinomycin C production in Streptomyces chrysomallus.

Three distinct classes of mutations affecting the biosynthesis of actinomycin have been established in Streptomyces chyrsomallus by crossing various actinomycin-nonproducing mutants with each other by protoplast fusion. In crosses between members of different classes of mutations, actinomycin-producing recombinant progeny arose, whereas in crosses between members of the same class, no actinomycin-producing recombinants were seen. Biochemical examination of a number of mutants revealed that the expression of all actinomycin synthetases was reduced by about 1 order of magnitude in mutants belonging to class II. In mutants of class I, the specific activities of the actinomycin synthetases were comparable with those measured in their actinomycin-producing parents. Feeding experiments with 4-methyl-3-hydroxyanthranilic acid (4-MHA), the biosynthetic precursor of the chromophore moiety of actinomycin, with representative mutants of the three genetic classes revealed formation of actinomycin in minute amounts by mutants of class I. It is suggested that mutants belonging to class I are mutated at a genetic locus involved in the biosynthesis of 4-MHA. Mutants belonging to class II appear to carry mutations at a locus involved in the regulation of the expression of the actinomycin synthetases. The role of the locus in class III mutations could not be assigned. Mapping studies in S. chrysomallus based on conjugal matings revealed the chromosomal linkage of all three loci. Mutations belonging to classes I and III were closely linked. Their genetic loci could be localized in a map interval of the chromosomal linkage group which is significantly distant from the gene locus represented by mutations belonging to class II.

Dactinomycin↗
PubMedDate not supplied

[1H-NMR analysis of heteroassociation of caffeine with antibiotic actinomycin D in the aqueous solution].

The molecular basis of the action of caffeine as a complex forming agent, an interceptor of aromatic drugs intercalating into DNA was studied by the example of the an anticancer antibiotic actinomycin D examined. The hetero-association of caffeine and actionomycin D was studied by one- and two-dimensional 1H-NMR spectroscopy (500 MHz). Concentration and temperature dependences of the proton chemical shifts of molecules in aqueous solution were measured. The equilibrium reaction constant of hetero-association of caffeine with actinomycin D (K = 246 +/- 48 M-1), the limiting chemical shifts of caffeine protons in complexes were determined. The most favourable structure of the 1:1 caffeine-actinomycin D hetero-complex in aqueous solution was constructed using the calculated values of the induced proton chemical shifts of molecules and the quantum-mechanical iso-shielding curves for caffeine and actinomycin D. The thermo-dynamical parameters of the hetero-complex formation between caffeine and actinomycin D were also determined. The structural and thermo-dynamical analysis showed that dispersive forces and hydrophobic interactions play the major role in hetero-association of caffeine and actinomycin D in aqueous-salt solution. The relative content of different complexes in mixed solutions containing caffeine and actinomycin D was calculated and distinctive features of the dynamic equilibrium of caffeine-actinomycin D hetero-associates were revealed as a function of concentration and temperature. It is concluded that hetero-association of caffeine and actinomycin D molecules a lowers the effective concentration of the drug in solution and hence the pharmacological activity of actinomycin D.

Anti-Bacterial Agents↗
PubMed1981

[New actinomycin from Actinomyces sp. No. 2].

A new actinomycin was isolated from a mixture of actinomycins formed by Actinomyces sp. No. 2, an organism producing auranthin, an actinomycetous antibiotic. The peptide chains of the new actinomycin contain such amino acids as threonine, valine, proline and sarcosine in a ratio of 2 : 4 : 2 : 2. N-Methyl-valine characteristic of all actinomycins is replaced in position 5 of both pentapeptide chains of the new actinomycin by valine. The new actinomycin is actinomycin D undermethylated in position 5 by valine. When the growing culture of Actinomyces olivobrunneus producing actinomycin D was exposed to sulfadimesine, an inhibitor of biological methylation, production of actinomycin D0 (sarcosine replaced by glycine in one of the pentapeptide chains) markedly increased, which indicated impairment of the glycine residue methylation. Still, no impairment of the valine residue methylation in position 5 of the pentapeptide chains was observed an no actinomycin with N-methyl-valine replaced by valine was formed.

Actinomyces↗
PubMedDate not supplied

Actinomycin D is an effective adjunctive immunosuppressive agent in recurrent cardiac allograft rejection.

BACKGROUND: Actinomycin D is a potent cytotoxic agent which inhibits DNA transcription by DNA-dependent RNA polymerases and has previously been used as adjunctive immunosuppressive agent for refractory renal allograft rejection. METHODS: To assess the efficacy of actinomycin D in cardiac allograft rejection, we studied seven patients with recurrent cellular or humoral rejection. All patients received intravenous actinomycin D 5 micrograms/kg every 6 weeks. RESULTS: During the 6-months after initiation of actinomycin D treatment, the mean number of treated cellular or humoral rejection episodes per patient (0.14) and the mean number of International Society for Heart and Lung Transplantation grade 2 or higher endomyocardial biopsy specimens per patient (0.3) were lower compared with those observed during the 6-month pre-actinomycin D period (1.6 and 2.6, respectively). By 6 months after initiation of actinomycin D, all seven patients were receiving lower daily maintenance doses of corticosteroids. The mean total corticosteroid dose after actinomycin D administration per patient per month (615 +/- 177 mg) was significantly lower than the pre-actinomycin D dose (1012 +/- 347 mg; p = 0.019). No patient had significant adverse effects. CONCLUSIONS: Actinomycin D is an effective immunosuppressive agent for prevention of recurrent cellular or humoral rejection after cardiac allograft rejection. The corticosteroid sparing effect of actinomycin D may be of particular benefit.

Biopsy↗
PubMed1992

Cycloheximide protection against actinomycin D cytotoxicity.

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.

Animals↗
PubMed1991

Effects of actinomycin D on airway constriction induced by tachykinins and capsaicin in guinea-pigs.

The effects of actinomycin D on airway constriction induced by tachykinins was studied in guinea-pigs in vitro and in vivo. Actinomycin D significantly inhibited the constriction of isolated guinea-pig trachea induced by neurokinin A (NKA) and eledoisin. Conversely, substance P (SP)- and physalaemine-induced constrictions were not affected by actinomycin D. The same selectivity in the inhibitory action of actinomycin D against tachykinins was also observed in in vivo. Actinomycin D given i.v. specifically inhibited the increase in airway resistance induced by NKA. I.v. injection of NKA caused not only airway constriction but also transient systemic hypotension. Interestingly, actinomycin D injected i.v. inhibited only airway constriction and the systemic hypotension induced by NKA was not affected. These results clearly suggest that actinomycin D specifically inhibits NKA-induced airway constriction in guinea-pigs. Actinomycin D also had an inhibitory action on the airway constriction induced by capsaicin. In the case of capsaicin-induced constriction, actinomycin D was more effective on the later phase of constriction than on the acute phase. The airway constriction induced by capsaicin is thought to be mediated by the release of SP and NKA from sensory nerve endings, and the persistent increase in airway resistance induced by capsaicin is thought to be due mainly to NKA.

Airway Resistance↗
PubMed1989

The expression of the TMV-specific 30-kDa protein in tobacco protoplasts is strongly and selectively enhanced by actinomycin.

The TMV-encoded 30-kDa protein has been implicated in the cell-to-cell transport of TMV in the infected plant. The polyethylene glycol-mediated inoculation of tobacco protoplasts with TMV particles and TMV RNA was used to compare the time courses of the viral 30-kDa protein synthesis in vivo. Upon infection of protoplasts with TMV RNA, the synthesis of the viral 30-kDa protein starts after 4 to 6 hr, has its maximum after 8 to 10 hr, and decreases. After inoculation of protoplasts with TMV, however, the start of the viral 30-kDa protein synthesis and its maximum are delayed by 2 hr, followed by the same decrease. We show that actinomycin D dramatically stimulates the synthesis of the 30-kDa protein by up to 2 orders of magnitude, whereas the synthesis of the viral 126 kDa, the 183 kDa, and the coat protein is increased only by a factor of 2. Surprisingly, actinomycin V is twice as active as actinomycin D, whereas actinomycin I is nearly inactive. The specific stimulation of the 30-kDa synthesis by actinomycin D in vivo depends neither on the Nicotiana variety nor on the TMV strain used. Final evidence that the 30-kDa protein is truly TMV-derived is provided by the slightly different electrophoretic mobilities of the 30-kDa proteins encoded by TMV strains vulgare, dahlemense, and U2. The identification of the 30-kDa protein in two-dimensional gels was achieved for the first time by a combination of ionic and nonionic detergents for the solubilization of the 30-kDa protein and by the specific stimulation of its synthesis by actinomycin D. The mechanism of the strong and selective actinomycin effect on the viral 30-kDa protein synthesis in vivo is as yet obscure. Actinomycin does not appear to act directly on viral protein biosynthesis, since it neither stimulates the 30-kDa synthesis upon translation of TMV RNA in vitro nor alters the ratio of the products. Actinomycin may rather act by inhibiting selectively the synthesis of a host factor whose synthesis starts at least 4 hr after TMV infection and which strongly inhibits the expression of the viral 30-kDa transport protein.

Capsid Proteins↗
PubMed1994

Binding of actinomycin D to the T(G)nT motif of double-stranded DNA: determination of the guanine requirement in nonclassical, non-GpC binding sites.

Strong binding of the antitumor antibiotic actinomycin D to the sequence 5'-TGGGT-3' in double-stranded DNA was recently established by equilibrium binding studies (Bailey et al., 1993). Actinomycin D binding to this -TGGGT- containing sequence was shown to be comparable to that of an -XGCY- containing oligonucleotide (Ka approximately 10(6) M-1). Investigation of -TGGGT- as a high-affinity binding site for actinomycin D follows from our 1989 sequencing study (Rill et al., 1989) in which the photoaffinity analog of actinomycin D (7-azidoactinomycin D) was used to determine DNA base sequence specificities and neighboring base effects. The studies presented here examine the guanine requirements for actinomycin D binding to such nonclassical (non-dGpC) sites by varying the number of central guanine residues in a series of selected duplex oligonucleotides. The central -T(G)nT- motif varies from n equals 1 to 4. Actinomycin D binding to each of these undecamers is characterized and correlated with binding to oligonucleotides of identical length and similar sequences that contain classical dGpC binding sites. Binding affinities of actinomycin D to this series of oligonucleotide duplexes (10 degrees C) can be summarized as -TGGGT- > -TGGT- > TGGGGT- > -TGT. The kinetics of SDS-induced dissociation of actinomycin D from these oligonucleotides reveal single-exponential decays with duration dependent on the sequence at the binding site. With the exception of the -TGGGT- containing oligomer, dissociation times for the T(G)nT duplexes were drastically different and much shorter than times obtained for the dissociation of actinomycin D from oligonucleotides having classical dGpC sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed2006

Actinomycins with altered threonine units in the beta-peptidolactone.

Five new members of the actinomycin family, actinomycins G2-G6 (2-6), are produced by Streptomyces iakyrus strain DSM 41873. Their structures were established by spectroscopic methods. Unlike actinomycin D (1), the alpha-ring of the novel compounds contains the unusual amino acid 3-hydroxy-5-methylproline, while the beta-ring includes N-methylalanine and either a chlorinated or hydroxylated threonine moiety. The chlorine-containing actinomycin G2 (2) is the main product; it exhibits strong cytotoxic and antibacterial activities. Actinomycin G5 (5) is the first actinomycin with an additional ring closure between the beta-peptidolactone and the actinoyl chromophore. Actinomycin G6 (6) resulted from the 4-hydroxythreonine-containing actinomycin G3 (3) by a 2-fold acyl shift of the beta-unit, which has not been observed before for this class of chromopeptides. The structural modification of compounds 5 and 6 goes along with an evident reduction of the biological activity. The biosynthesis of aniso-actinomycins is discussed.

Bacillus subtilis↗
PubMed1988

Metabolic regulation in Streptomyces parvulus during actinomycin D synthesis, studied with 13C- and 15N-labeled precursors by 13C and 15N nuclear magnetic resonance spectroscopy and by gas chromatography-mass spectrometry.

Recent studies have suggested that the onset of synthesis of actinomycin D in Streptomyces parvulus is due to a release from L-glutamate catabolic repression. In the present investigation we showed that S. parvulus has the capacity to maintain high levels of intracellular glutamate during the synthesis of actinomycin D. The results seem contradictory, since actinomycin D synthesis cannot start before a release from L-glutamate catabolic repression, but a relatively high intracellular pool of glutamate is needed for the synthesis of actinomycin D. Utilizing different labeled precursors, D-[U-13C]fructose and 13C- and 15N-labeled L-glutamate, and nuclear magnetic resonance techniques, we showed that carbon atoms of an intracellular glutamate pool of S. parvulus were not derived biosynthetically from the culture medium glutamate source but rather from D-fructose catabolism. A new intracellular pyrimidine derivative whose nitrogen and carbon skeletons were derived from exogenous L-glutamate was obtained as the main glutamate metabolite. Another new pyrimidine derivative that had a significantly reduced intracellular mobility and that was derived from D-fructose catabolism was identified in the cell extracts of S. parvulus during actinomycin D synthesis. These pyrimidine derivatives may serve as a nitrogen store for actinomycin D synthesis. In the present study, the N-trimethyl group of a choline derivative was observed by 13C nuclear magnetic resonance spectroscopy in growing S. parvulus cells. The choline group, as well as the N-methyl groups of sarcosine, N-methyl-valine, and the methyl groups of an actinomycin D chromophore, arose from D-fructose catabolism. The 13C enrichments found in the peptide moieties of actinomycin D were in accordance with a mechanism of actinomycin D synthesis from L-glutamate and D-fructose.

Chemical Phenomena↗
PubMed1979

Comparison of avidin induction in the differentiated and undifferentiated chick oviduct by progesterone, actinomycin D and oviductal injury.

Various oestrogen (diethylstilboestrol, DES) pre-treatments were carried out on chicks and the production of avidin in the oviduct was induced by progesterone, actinomycin D or oviductal injury. Avidin induction was dose-dependent at doses between 5 mg and 40 mg progesterone/kg or 50 micrograns and 300 micrograms actinomycin D/kg respectively. The induction by oviductal injury correlated with the magnitude of tissue injury. First signs of avidin induction were seen at 4 h after oviductal injury, 12 h after progesterone or 12--16h after actinomycin D administration. Actinomycin D (200 micrograms/kg), when administered after progesterone injection, did not increase avidin induction by progesterone, this indicating that avidin induction by actinomycin D is not a "superinduction" effect. Evidence is presented here that the mechanism of avidin induction by oviductal injury and actinomycin D differs from that by progesterone. The differentiation of the oviduct caused by DES treatment was necessary for the induction by progesterone, whereas actinomycin D and oviductal injury also induced avidin in the undifferentiated or poorly differentiated oviduct. Simultaneous DES stimulation potentiated induction by progesterone but not by actinomycin D or oviductal injury. Furthermore, single prior DES stimulation increased avidin induction in the differentiated oviduct of DES-withdrawn chicks caused by progesterone but not that by actinomycin D or oviductal injury.

Animals↗
PubMed2005

[Actinomycin D and its mechanisms of action].

Actinomycin D is a well-known antibiotic of the actinomycin group that exhibits high antibacterial and antitumor activity. Actinomycin D has been widely used in clinical practice since 1954 as an anticancer drug for treating many tumors and it is also a useful tool in biochemistry and molecular biology. According to the Internet bibliographic database -- MEDLINE, actinomycins, and mainly actinomycin D, have been the subject of about 3300 science papers so far, and this paper is a review of the information concerning the mechanisms of action of actinomycin D. There are several mechanisms of its action that are responsible for its cytotoxic and antitumor action, these being associated with DNA functionality, leading to RNA and, consequently, protein synthesis inhibition. The two main mechanisms are intercalation to DNA and the stabilization of cleavable complexes of topoisomerases I and II with DNA, in which a phenoxazone ring localizes between GpC base pair sequence in DNA and polypeptide lactones rings occupy a position in the minor groove of the DNA helix or the drug penetrates to a place in the DNA structure where topoisomerase binds with DNA, respectively. Moreover, the slow dissociation of actinomycin D from DNA complexes, its photodynamic activity and free radical formation, as well as other biochemical effects of activity of actinomycin D may be, as suggested, important factors that influence the biological activity of this drug. In the literature not enough convincing evidence has been proposed that could indicate one particular mechanism of action as responsible for the biological activity of actinomycin D.

Animals↗