Disease relevance of acridine

• Pancreatic acinar cells were isolated at different times after induction of pancreatitis and incubated with 50 microM of acridine orange to identify acidic intracellular compartments [1].
• Acridine orange-DNA complex in actinic keratosis [2].
• Acridine-induced frameshift mutagenesis in bacteriophage T4 has been shown to be dependent on T4 topoisomerase [3].
• We previously reported the bioactivity of acridine-based compounds against PrP(Sc) replication in scrapie-infected neuroblastoma cells and now report the improved potency of bis-acridine compounds [4].
• Epicardial microvessels (25 to 130 microm), in focus throughout the cardiac cycle, were recorded after infusion of acridine orange (to fluorescently label leukocytes) during either 1 hour of ischemia followed by 2 hours of reperfusion, 3 hours of ischemia, or 3 hours of no ischemia [5].

Psychiatry related information on acridine

• Investigations were carried out on the spectral characteristics, order of addition of reagents, selection of the buffer system, effect of pH, influence of reaction time, effect of salt, the usage of reagents, interference of foreign substances and the effect of different acridine derivatives [6].
• The acridine-based, potential Alzheimer's disease therapeutic agents, tacrine and velnacrine, were incubated with rat or gerbil neocortical synaptosomal membranes [7].
• The binding of acridine orange to single-stranded polyribonucleic acid at low polymer to dye ratios exhibits cooperative behavior of the kind observed with other simple polyanions [8].

High impact information on acridine

• Longer-term studies using cells preincubated with acridine orange indicated that phagolysosomes containing live Histoplasma continued to maintain a relatively neutral pH for at least 30 h [9].
• Isolated cells were cultured for 48 h in the presence of a variety of TNP conjugates including TNP-Brucella abortus (Ba), TNP-Ficoll, TNP-sheep erythrocytes (SRBC), TNP-human gamma globulin (HGG), or TNP-ovalbumin (OVA) before being harvested and subjected to acridine orange cell cycle analysis [10].
• METHODS: Cytotoxicity of the acridine mutagen 6-chloro-9-[3-(2-chloroethylamino)propylamino]-2-methoxy-acridine (ICR191), a DNA frameshift inducer, was determined in the mismatch repair-deficient human colon carcinoma cell line HCT116 versus the repair-reconstituted derivative HCT116+C3 [11].
• PMNL were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in culture, and examined for the morphologic changes of apoptosis and viability by fluorescent microscopy [12].
• Throughout development of pancreatitis, vacuoles accumulated acridine orange indicating an acidic interior [1].

Chemical compound and disease context of acridine

• Thymidylate synthase (5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) from methotrexate-resistant Streptococcus faecium has a UV absorbance peak at 259 nm and stains with acridine orange because of the presence of RNA on the protein [13].
• The antibodies elicited by the quinacrine-protein conjugates in ascites tumor-bearing mice substantially neutralized the antitumor effectiveness of the low dosages (0.5 to 2.0 mumol/kg) of the acridine nitrogen mustards that were required for a demonstration of chemotherapeutic activity [14].
• The acridine derivative amsacrine (m-AMSA) is used clinically for the treatment of acute leukemias [15].
• 1. Acridine Orange inhibits growth of Escherichia coli K12 when incubated at pH 7.9, but not at pH 7.4 [16].
• Fluorescent probes for lysosomes (acridine orange) and mitochondria (rhodamine 123) confirmed that cisplatin's toxicity to RPTCs was delayed and cumulative [17].

Biological context of acridine

• Counts of particles internalized and assessment of acidification of the phagosomes by acridine orange staining indicated that Na+/K+ fluxes were not necessary for phagocytosis or phagosomal acidification in J774.2 macrophages [18].
• Exocytosis resulted in the release of acridine orange which was visible as a disappearance of labeled vesicles and, under optimal conditions, produced light flashes by fluorescence dequenching [19].
• The intercalated acridine extended by 2 base pairs the region of the duplex protected by the oligopyrimidine against degradation by the nuclease activity of the copper phenanthroline chelate [20].
• In the absence of a functional T4 topoisomerase, in vivo acridine-induced mutagenesis is reduced to background levels [3].
• These correlations suggest that acridine-induced discontinuities introduced by topoisomerase could be processed into frameshift mutations [3].

Anatomical context of acridine

• We have previously shown that flow cytometric analysis of acridine orange-stained bone marrow cells is useful for the objective enumeration and characterization of plasma cells from patients with myeloma, frequently exhibiting an abnormal DNA and an elevated RNA content [21].
• The present studies examined the rate of Na+/H+ exchange (acridine orange method) and Na+/HCO3 cotransport (22Na uptake) in apical and basolateral membranes prepared from the rabbit renal cortex by sucrose density gradient centrifugation [22].
• We therefore have utilized acridine orange, a fluorescent weak base, to study the number and distribution of acidic vesicles of rat hepatocytes in primary culture and compared these with the number and distribution of lysosomes and other storage vesicles [23].
• Zymogen granules released acutely from hypotonically disrupted cells without homogenization also accumulated acridine orange [24].
• Secretory vesicles were preloaded with acridine orange in intact cells, and the cells were sonicated to produce flat, carrier-supported plasma membrane patches with attached vesicles [19].

Associations of acridine with other chemical compounds

• Addition of a protonophore (10 microM monensin or 5 microM carbonyl cyanide m-chlorophenylhydrazone [CCCP] or a weak base (5 mM NH4Cl) completely and rapidly abolished acridine orange fluorescence inside both zymogen granules and vacuoles providing further evidence for an acidic interior [1].
• We observed in the cytoplasm abundant round vacuoles with diameters up to 2 microns that concentrated acridine orange by a process inhibited by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) [25].
• The trapping of the weak bases, acridine orange or 3-(2,4 dinitro anilino)-3'-amino-N-methyl dipropylamine (DAMP), within the granules was used to evaluate delta pH [26].
• Our data suggest that bis-acridine analogs may provide a potent alternative to the acridine-based compound quinacrine, which is currently under clinical evaluation for the treatment of prion disease [4].
• The benzo[a]pyrene oxides were inactive in a strain (TA1535) that is reverted by base pair mutagens such as N-methyl-N'-nitro-N-nitrosoguanidine or in a strain (TA1536) that detects framshift mutagens similar to the acridine half-mustard ICR-191 [27].

Gene context of acridine

• Moreover, inhibition of MDM2 using antisense ODNs also triggered MM cell apoptosis as evidenced by acridine orange-ethidium bromide staining [28].
• TUNEL assay and Acridine Orange staining revealed that in the absence of tfap2a a subset of neural crest cells are unable to undergo terminal differentiation and die by apoptosis [29].
• Acridine derivatization did not impair the exquisite target specificity of triplex formation, since the derivatized oligonucleotide inhibited the binding of nuclear proteins to the overlapping NF kappa B enhancer sequence on an IL-2 R alpha target and not on the related human immunodeficiency virus long terminal repeat target [30].
• Enforced expression of C22orf3 in AtT20 cells had no measurable effects on cell proliferation or viability; however, in response to bromocriptine challenge (10-40 microm) cells expressing this gene showed a significantly augmented apoptotic response as determined by both acridine orange staining and TUNEL labeling [31].
• WST-1 conversion assays and acridine orange staining showed that vector-transfected control cells were killed by TNF-alpha or anti-Fas antibody in a dose-dependent manner, whereas BHRF1-expressing cells were resistant to apoptosis induced by these mediators [32].

Analytical, diagnostic and therapeutic context of acridine

• Cells were stained with acridine orange, and both RNA and DNA content were determined by flow cytometry [33].
• Electron microscopy processing and staining of nuclei were used to localize reaction products of acridine orange staining in actinic keratosis of human skin [2].
• A rapid diagnostic test for malaria based on acridine orange staining of centrifuged parasites in a microhaematocrit tube ('QBC' tube) was compared with the thick blood smear in 12 volunteers experimentally infected with Plasmodium falciparum, 408 residents of a malaria endemic area, and 180 hospital patients with suspected malaria [34].
• The purified antibodies stained an acidic vacuolar compartment as shown by double-labeling experiments with acridine orange and indirect immunofluorescence [35].
• The lysosome localization was demonstrated by indirect immunofluorescent staining, co-localization of the antigen to sites of acridine orange uptake, and immunoelectron microscopy [36].

References