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Methods in Molecular Medicine 2003
Review
Topics: Animals; Annexin A5; Apoptosis; Cell Membrane; Cell Membrane Permeability; Cysteine Endopeptidases; DNA Damage; DNA Fragmentation; DNA, Neoplasm; Dactinomycin; Enzyme Activation; Flow Cytometry; Fluorescent Dyes; Humans; In Situ Nick-End Labeling; Neoplasms; Nephelometry and Turbidimetry; Nucleic Acid Denaturation
PubMed: 12710217
DOI: 10.1385/1-59259-380-1:323 -
Postepy Higieny I Medycyny... 2005Actinomycin 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... (Review)
Review
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.
Topics: Animals; Antibiotics, Antineoplastic; DNA; Dactinomycin; Humans
PubMed: 15995596
DOI: No ID Found -
Medical and Pediatric Oncology May 1995Dactinomycin-induced cutaneous toxicity is rare in pediatric patients not receiving radiation therapy. We describe dactinomycin-related lesions in the axilla, groin, and...
Dactinomycin-induced cutaneous toxicity is rare in pediatric patients not receiving radiation therapy. We describe dactinomycin-related lesions in the axilla, groin, and central line exit site of two children treated for rhabdomyosarcoma, neither of whom had received radiation treatment. One patient was initially treated with systemic antifungal therapy, and developed recurrent lesions on reexposure to the drug. The other was noted to have mild, diffuse hyperpigmentation. Skin biopsies revealed interface dermatitis with syringometaplasia in both cases. Both children recovered uneventfully within 4 weeks. Recognition of unusual rashes with a characteristic distribution in patients receiving dactinomycin should aid in diagnosis, and help avoid unnecessary therapeutic procedures.
Topics: Child; Child, Preschool; Dactinomycin; Drug Eruptions; Female; Humans; Male; Rhabdomyosarcoma, Alveolar
PubMed: 7700187
DOI: 10.1002/mpo.2950240512 -
JAMA Apr 1966
Clinical Trial
Topics: Clinical Trials as Topic; Dactinomycin; Humans; Wilms Tumor
PubMed: 4286315
DOI: 10.1001/jama.1966.03100170095031 -
Toxicology 1975Intratracheal (i.t.) administration of protein synthesis inhibitors produced pulmonary edema. Of those inhibitors studied, dactinomycin (act. D) was the most potent....
Intratracheal (i.t.) administration of protein synthesis inhibitors produced pulmonary edema. Of those inhibitors studied, dactinomycin (act. D) was the most potent. Severity of lung damage due to act. D was dose- and almost age-related. Maximal intensity of pulmonary edema was reached on the 3rd day following administration and remained constant for 14 days. Histopathological studies revealed confluent edema of the entire lung. Pretreatment with act D induced tolerance to an LD100 edematogenic dose of thiourea. The effects of i.t. instillation of act. D appear to be localized in the pulmonary tissue. Lung lavage fluid collected from drug-treated rats had higher acid and alkaline phosphatase activities, higher protein content and more leukocyte infiltration than that of control.
Topics: Animals; Dactinomycin; Drug Tolerance; Intubation, Intratracheal; Liver; Lung; Male; Phosphoric Monoester Hydrolases; Protein Biosynthesis; Pulmonary Edema; Rats; Thiourea; Time Factors
PubMed: 165594
DOI: 10.1016/0300-483x(75)90021-9 -
IARC Monographs on the Evaluation of... 1976
Review
Topics: Animals; Carcinogens; Dactinomycin; Drug Evaluation, Preclinical; Female; Hyperplasia; Male; Mice; Mitosis; Necrosis; Rabbits; Rats; Sarcoma; Skin; Transcription, Genetic
PubMed: 62702
DOI: No ID Found -
Biochimica Et Biophysica Acta Jan 1993A novel actinomycin (Act SG3) from a strain of Streptomyces galbus var. C-72, as well as actinomycin D (Act D) were found to act as competitive inhibitors of serine... (Comparative Study)
Comparative Study
A novel actinomycin (Act SG3) from a strain of Streptomyces galbus var. C-72, as well as actinomycin D (Act D) were found to act as competitive inhibitors of serine proteinases from microorganisms. The inhibitory properties of Act SG3 and Act D are compared with these of other peptide antibiotics, namely bacitracin A (Bac A) and gramicidin S (Gr S). The last compound has only a weak inhibitory effect. The following order of affinity for the four peptide antibiotics towards subtilisin DY and proteinase K was observed: Bac A > Act D > Act SG3 = Gr S. The affinity towards thermitase changes as follows: Act SG3 = Act D > Bac A > Gr S.
Topics: Amino Acids; Binding, Competitive; Dactinomycin; Endopeptidase K; Kinetics; Protease Inhibitors; Serine Endopeptidases; Streptomyces; Subtilisins
PubMed: 7678503
DOI: 10.1016/0167-4838(93)90194-v -
Tetrahedron Letters Jul 1966
Topics: Bacillus subtilis; Dactinomycin
PubMed: 4163016
DOI: 10.1016/s0040-4039(01)82834-3 -
Journal of Immunological Methods Jul 2002Apoptosis and primary necrosis are the two modes of cell death induced by a lethal injury. The majority of structural and biochemical events occurring during cell death... (Review)
Review
Apoptosis and primary necrosis are the two modes of cell death induced by a lethal injury. The majority of structural and biochemical events occurring during cell death can be analysed by flow cytometry. The 7-aminoactinomycin D (7-AAD) assay can be used to detect the loss of membrane integrity during apoptosis of murine thymocytes and human peripheral lymphocytes. We describe here new applications of the 7-AAD assay. It can be applied to a variety of cell lines of different origins, including adherent cell lines, and it allows the co-detection of lipidic antigens such as phosphatidylserine (PS) residues, and biochemical processes linked to apoptosis, such as the loss of mitochondrial transmembrane potential, cardiolipin peroxidation, the expression of the 7A6 mitochondrial antigen and DNA fragmentation. Thus, this assay is a noninvasive method particularly adapted to the analysis of biochemical events associated with cell death. Finally, we show that this assay is not specific for apoptosis since it detects oncosis, the early stage of primary necrosis.
Topics: Apoptosis; Caspases; DNA Fragmentation; Dactinomycin; Flow Cytometry; Humans; Jurkat Cells; Mitochondria; T-Lymphocytes
PubMed: 12072180
DOI: 10.1016/s0022-1759(02)00072-8 -
Acta Chimica Slovenica Jun 2022DNA thermal denaturation was evaluated as a measure of the effect of antitumor drug actinomycin D on the stability of the double helix and also the effect of SDS...
DNA thermal denaturation was evaluated as a measure of the effect of antitumor drug actinomycin D on the stability of the double helix and also the effect of SDS micelles on actinomycin D - DNA complexes. The results indicated that the melting temperature of DNA was dependent on drug concentration, increasing with actinomycin D concentration. High thermal stabilization (about 10 °C) of the DNA helix after the association with actinomycin D clearly demonstrates the intercalative binding mode. The presence of SDS micelles leads to the release of intercalated actinomcyin D molecules from DNA double helix and their further relocation in surfactant micelles. These results highlighted that the drug release can be controlled in time and by varying the concentration and nature of surfactant.
Topics: DNA; Dactinomycin; Micelles; Surface-Active Agents; Temperature
PubMed: 35861079
DOI: 10.17344/acsi.2021.7189