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At least 19 recordsLinked to original sources
PubMed1976

Aggregation of acridine orange: crystal structure of acridine orange tetrachlorozincate 2C17H19N3-2HCl-ZnCl2-CH3COOH.

The crystal structure of the biological stain, "acridine orange," has been determined. This compound, when crystallized from ethanol, is shown to be a zinc chloride double salt of acridine orange, containing, in addition, acetic acid of crystallization. These additional components are residuals from the method of preparation of acridine orange. This complex, 2 acridine orange-2HCl-ZnCl2-CH3COOH, (2C17H19N3-2HCl-ZnCl2-CH3COOH) crystallizes in the monoclinic space group P21, a = 9.965 (2), b = 21.507 (6), c = 9.645 (2) A, beta = 113.98 degrees (2), V = 1888.7 (8) A3, FW = 800.0, Z = 2, DX = 1.41 g-cm-3, Dobs = 1.43 (9) g-cm-3. Three-dimensional diffraction data were collected with CuKalpha radiation, and the structure refined to R = 0.065 for 1885 observed reflections. In the crystal structure hydrogen bonds are formed, via the protonated nitrogen atom of the central rings of two acridine orange cations, to two chloride ions in a ZnCl42- tetrahedral grouping. These two acridine orange molecules are stacked in parallel planes, approximately 3.4 A apart, with the long axes of the ring systems inclined at 26.5 to each other. Thus an apparent dimerization of the acridine, orange is facilitated by the anions present, resulting in the complex studied. The two -N(CH3)2 groups of each acridine orange molecule are not protonated in this crystalline form. The mode of molecular packing found here may be relevant to models for the external stacking of acridine orange around a DNA molecule. The importance of removing any zinc salt from acridine orange preparations prior to aggregation studies is stressed.

Acridines↗
PubMedDate not supplied

Thiol-disulfide status and acridine orange fluorescence of mammalian sperm nuclei.

The relationship between thiol-disulfide status and acridine orange fluorescence of testicular, epididymal, and ejaculated spermatozoa in several mammalian species was investigated. Spermatozoa were fixed with acetic alcohol, stained with acridine orange, and examined with a fluorescence microscope. The majority of the nuclei of testicular spermatozoa of the hamster, mouse, and rabbit exhibited red acridine orange fluorescence. The proportion of sperm nuclei with red acridine orange fluorescence decreased as the spermatozoa descended the epididymis. Red acridine orange fluorescence was replaced by green acridine orange fluorescence. The site in the epididymis where 100% of the nuclei exhibited green fluorescence was the distal caput in the mouse, the corpus in the rabbit, and the proximal cauda in the hamster. In semen samples from men with proven fertility, normal semen parameters, or both, about 60% to 90% of the nuclei exhibited green acridine orange fluorescence. The proportion of sperm nuclei exhibiting green acridine orange fluorescence was higher in the spermatozoa pellet (containing highly motile spermatozoa) obtained by centrifugation through a Percoll gradient. From experiments using disulfide-reducing, thiol-oxidizing and thiol-detecting agents, we concluded that sperm nuclei fluoresce red when they are treated with acid while their DNA-associated protamines are poor in disulfides. Under such conditions, DNA is vulnerable to denaturation. Acridine orange binds to denatured (single-stranded) DNA as aggregates and emits red fluorescence. In contrast, when sperm nuclei are treated with acid while their DNA-associated protamines are rich in disulfides, DNA is resistant to denaturation. Acridine orange binds to native (double-stranded) DNA as a monomer and emits green fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridine Orange↗
PubMed1979

Photodynamic effects of dyes on bacteria. II. Genetic effects of broad-spectrum visible light in the presence of acridine dyes and methylene blue in chemostat cultures of Escherichia coli.

Photodynamic mutagenesis was studied in chemostat cultures of Escherichia coli B/r (TlR trp) exposed to one of six different acridine dyes or methylene blue. Mutation to phage T5 resistance was induced with a broad-spectrum fluorescent-light source. All of the agents tested were photomutagenic; acridine yellow was the most efficient sensitizer and quinacrine was the least efficient. Quinacrine also was moderately mutagenic in the dark, in contrast to the other agents tested, which were not significantly mutagenic in the dark at the low concentrations tested for photomutagenesis. The mutation rate with acridine orange was directly proportional to both fluence rate and dye concentration over the ranges tested. Photomutation rates with acridine orange, proflavine and methylene blue were independent of growth rate of the chemostat cultures. These results are consistent with photomutagenesis occurring as the result of photochemical damage to DNA-dye complexes, independent of cell expression was approximately 2.5 generations for each of the photomutagens tested. This short expression delay supports an earlier segregational model for expression of phage resistance. The following results suggest that photodynamic mutagenesis is due mainly to intercalated dye molecules: (1) both acridine and 9-aminoacridine are photodynamic mutagens; (2) acridine inhibits photomutagenesis with acridine orange; and (3) neither putrescine or spermine, which bind to DNA without intercalating, inhibited photomutagenesis by acridine orange or proflavine.

Acridines↗
PubMed1976

DNA polyintercalating drugs. Proton magnetic resonance studies of a new acridine dimer. Conformations and interactions with mono- and dinucleotides.

The conformation in aqueous solution of one acridine dimer which is able to bisintercalate in DNA (1, 14-bis(5-methoxy-6-chloro-9-acridinyl)-1,5,10,14-tetraazatetradecane tetrahydrochloride) (AcDi) and its interactions with mono- and dinucleotides have been investigated by fast Fourier transform proton magnetic resonance spectroscopy. Variations in chemical shifts of the most distingusihable protons of the acridine dimer with temperature bring evidence of a folded in equilibrium unfolded fast conformational equilibrium in the temperature range of 4-85 degrees C. Equilibrium parameters were estimated. The folded conformation has been deduced from iso-shielding curves of the acridine ring. In the complex between AcDi and 3'- or 5"AMP, and adenine ring is intercalated between the two acridine rings to give a sandwich-like complex. Studies of the interaction with adenylyl(3' leads to 5') adenosine (ApA) show two different complexes in equilibrium with the 3' or 5' moiety of ApA intercalated in the acridine dimer. These conclusions are derived from comparative studies with 2-methoxy-6-chloro-9-(3-dimethylaminopropylamino)acridine dihydrochloride which is the corresponding acridine monomer-(AcMo). In that case the self-association constant was determined. A model of the AcMo-5'-AMP complex was deduced from the analysis of the chemical shifts of the adenine protons. In this model, the N10+-D bond of the acridine points toward the negatively charged phosphate of the nucleotide.

Acridines↗
PubMed1975

[Factors influencing transduction of genetic determinants of penicillinase activity and pathogenicity in staphylococcus aureua. II. Antiphage activity of acridine derivatives].

Acridine dyes examined earlier (acrichine, acridine orange, proflavine and rivanol) and newly-synthesized preparations (acridines No. No. 37--40) were studied in the capacity of nonspecific agents influencing the lytic cycle in development of staphylococcus phages. Acrichine and acridine No. 37 failed to prevent lysis of the indicator staphylococcus cultures (strains 16/160 and 8325) by bacteriophages; proflavine, rivanol, acridines No. No. 39--40 produced a marked inhibitory effect; acridine orange and acridine No. 38 inhibited the staphylococcus lysis completely. Some preparations could be used to investigate the transduction phenomenon.

Acridines↗
PubMed1979

Relationship of carcinogenicity, mutagenicity, and K-region reactivity in benz[c]acridines.

Benz[c]acridine and its 10 methyl-substituted derivatives were examined for chemical reactivity with osmium tetroxide and mutagenic activity on Salmonella typhimurium, and the results were contrasted with the electronic charge in the K region and the carcinogenic activity of benz[c]acridines. The addition of osmium tetroxide took place at the K region of benz[c]acridines. A linear relationship was established between the charge in the K region and the rate constant of the second-order reaction between osmium tetroxide and benz[c]acridines except the 5,7-dimethyl derivative whose substituent in the 5-position sterically hindered the reaction. Benz[c]acridines showed mutagenic activity in the presence of S-9 Mix, but not in the absence of S-9 Mix. There was a corresponding relationship among the K-region reactivity, mutagenic activity, and carcinogenic activity in benz[c]acridines. The only exception for this was the 7,11-dimethyl derivative in which the 11-methyl group had a steric effect on the ring-nitrogen atom. It was suggested that a common mechanism with regard to the reactivity of the K region is working in both carcinogenesis and mutagenesis. It was concluded that benz[c]acridines are activated, before they display a carcinogenic or mutagenic activity, to a proximate form such as 5,6-epoxides, through a metabolic process in which the nucleophilic property of the K region to react with electrophilic reagents plays an important role.

Acridines↗
PubMed1992

Lysosomal storage of sulfated glycosaminoglycans in cultured fibroblasts exposed to immunostimulatory acridine derivatives.

The purpose of the present cytological and radiochemical study was to investigate whether the immunomodulatory agent 3,6-bis[2-(diethylamino)ethoxy]acridine (CL-90.100) and three congeners induce lysosomal storage of sulfated glycosaminoglycans (sGAG) in cultured rat corneal fibroblasts. The reason for asking this question was as follows: The four acridine derivatives have molecular similarities with the dicationic amphiphilic compound tilorone, which has previously been shown to cause sGAG storage in cultured cells and in intact rats. The cells were exposed to the drugs for 72 hr. Tilorone served as reference. All acridine derivatives caused cytological alterations which, on the basis of the cytochemical results, were indicative of lysosomal sGAG storage. The threshold concentrations ranged from 0.3 to 0.7 microM. Radiochemical experiments showed that CL-90.100 up to 10 microM induced [35S]GAG storage in a dose-dependent manner, with an EC50 of 2 microM. Concentrations above 10 microM were cytotoxic. Experiments with equimolar concentrations (3 microM) demonstrated that three of the acridine derivatives were more potent and one was less potent than tilorone. Additionally, CL-90.100 was tested on bovine corneal fibroblasts, with cytochemical and radiochemical results similar to those in rat cells. The present findings show that (a) the four acridine derivatives induce lysosomal sGAG storage; (b) the acridine ring, compared with the fenfluorenone ring (tilorone), enhances this potency; and (c) the substituents at the nitrogens can have some influence on the potency to induce sGAG storage.

Acridines↗
PubMed1992

10N-nonyl acridine orange interacts with cardiolipin and allows the quantification of this phospholipid in isolated mitochondria.

The acridine orange derivative, 10N-nonyl acridine orange, is an appropriate marker of the inner mitochondrial membrane in whole cells. We use membrane model systems to demonstrate that 10N-nonyl acridine orange binds to negatively charged phospholipids (cardiolipin, phosphatidylinositol and phosphatidylserine). The stoichiometry has been found to be 2 mol 10N-nonyl acridine orange/mol cardiolipin and 1 mol dye/mol phosphatidylserine or phosphatidylinositol, while, with zwitterionic phospholipids, significant binding could not be detected. The affinity constants were 2 x 10(6) M-1 for cardiolipin-10N-nonyl-acridine-orange association and only 7 x 10(4) M-1 for that of phosphatidylserine and phosphatidylinositol association. The high affinity of the dye for cardiolipin may be explained by two essential interactions; firstly an electrostatic interaction between the quaternary ammonium of nonyl acridine orange and the ionized phosphate residues of cardiolipin and secondly, hydrophobic interactions between adjacent chromophores. A linear relationship was demonstrated between the cardiolipin content of model membranes and the incorporated dye. Consequently, a convenient and rapid method for cardiolipin quantification in membranes was established and applied to the cardiolipin-containing organelle, the mitochondrion.

Acridine Orange↗
PubMed1978

A comparison of acridine orange and Feulgen cytochemistry of human tumor cell nuclei.

Specimens of cells derived from tumors of the human female genital tract plus normal cells as standards have been divided into aliquots and stained according to acridine orange or pararosanilin:Feulgen procedures. Acridine orange-stained cells were slit-scanned for 535 nm nuclear fluorescence; Feulgen-stained cells were comb-scanned for 580 nm nuclear absorbance. For each specimen examined, the tumor cell:normal cell ratio of mean nuclear fluorescence following acridine orange staining was greater than the tumor cell:normal cell ratio of mean nuclear absorbance following Feulgen staining. The tumor cell:normal cell ratio of mean nuclear fluorescence ranged from 2.3 for a nonkeratinizing squamous cell carcinoma to 3.9 for a keratinizing squamous cell carcinoma. The tumor cell:normal cell ratio of mean nuclear absorbance ranged from 1.4 for a mixed mesodermal sarcoma to 2.3 for a small cell squamous cell carcinoma. These results indicate that the elevated nuclear fluorescence intensity from acridine orange-stained tumor cells cannot be explained solely on the basis of elevated Feulgen:DNA content. An alternative hypothesis, consistent with these results, is that DNA is the principal binding substrate for intranuclear acridine orange and that the DNA of certain tumor cells is more accessible to acridine orange than is the DNA of normal cells.

Acridines↗
PubMed1979

Staining of DNA-phosphate groups with a mixture of azure A and acridine yellow.

This paper deals with staining of DNA-phosphate groups with a mixture of an equal parts of aqueous solution of azure A and acridine yellow in a 1:1 proportion and also embodies a study of the absorption properties of the stained nuclei. It also embodies results of sequential staining of nuclei stained first with azure A followed by staining with acridine yellow and vice versa, after extraction of RNA with cold phosphoric acid. The results indicate that the absorption peaks of nuclei differ from those of nuclei stained for DNA-aldehyde molecules with azure A-SO2 or acridine yellow-SO2. The in vitro absorption characteristics of an aqueous solution of azure A and those of an aqueous solution of acridine yellow are also presented herein. The conclusion obtained from this study is that all the phosphate groups of DNA do not take part in the staining process when staining is carried out with azure A or acridine yellow alone after after RNA has been extracted. This is because the nuclei stained with these dyes sequentially show the presence of acridine yellow-DNA and azure A-DNA complex.

Acridines↗
PubMed1991

Acridine orange as a probe for measuring pH gradients across membranes: mechanism and limitations.

Acridine orange is an optical probe commonly used to monitor pH gradients across membranes. In the present study, the changes observed in the visible absorption spectrum of acridine orange during intravesicular acidification of oat root plasma membrane vesicles are shown to be identical with those obtained by increasing the free dye concentration, adding anions, or lowering the temperature, but different from those obtained on addition of biological membranes. It is therefore suggested that the absorbance changes observed during the formation of the pH gradient are simply due to accumulation of free dye inside the vesicles and subsequent dimerization, and not the result of dye-membrane interactions. The proportion of monomeric acridine orange that could undergo dimerization decreased with decreasing temperature. Furthermore, in a membrane-free system different anions induced the formation of dimer-excimer complexes to different degrees. During the formation of the pH gradient permeant anions present in the reaction medium follow the movement of protons into the vesicles, and the intravesicular accumulation of anions thereby amplifies acridine orange quenching, the degree of amplification being dependent on the anion species. Therefore, the use of acridine orange, and probably all metachromatic dyes, as probes for monitoring pH gradients is limited, since these probes neither reflect quantitatively the amount of H+ pumped nor the effect of anions and temperature on transmembrane H+ transport.

Acridine Orange↗
PubMed1975

An acridine probe into the physiological state of the cell.

Acridine orange was used as a probe to look into the physiological state of the yeast cell, particularly as regards the change in the properties of the membrane (which acts as a barrier against the incoming acridine orange) and the availability of binding sites for acridine orange in chromosomal DNA during growth. After acridine orange had been introduced into the cell, the genetic change at a specific locus with incubation time was measured photodynamically. A three-fold increase in the rate of penetration of acridine orange into the cell was observed, for instance, in going from the resting phase to the dividing phase. A five-fold increase was observed in the number of binding sites in chromosomal DNA under the same transition of the cell. These two parameters may be useful as a measure of the physiological changes in the cell. Some environmental factors such as pH and temperature were also demonstrated to affect the parameters.

Acridines↗
PubMedDate not supplied

Stereochemistry of the major rat liver microsomal metabolites of the carcinogen 7-methylbenz[c]acridine.

The major metabolites of the carcinogen 7-methylbenz[c]acridine (7MBAC), trans-5,6-dihydro-5,6-dihydroxy-7-methylbenz[c]acridine (7MBAC-5,6-DHD), and trans-8,9-dihydro-8,9-dihydroxy-7-methylbenz[c]acridine (7MBAC-8,9-DHD) were characterized as their enantiomers after separation of their bis-(+)-(1R,2S,4S)-endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5 -ene-2-carboxylic acid [(+)-HCA] esters and hydrolysis. The synthetic precursor, trans-3,4-dihydroxy-7-methyl-1,2,3,4-tetrahydrobenz[c]acridine (7MBAC-3,4-THD), was similarly separated into enantiomers, and the dihydrodiol trans-3(S),4(S)-dihydro-3,4-dihydroxy-7-methylbenz[c]acridine (7MBAC-3,4-DHD) was prepared from 7MBAC-3(S),4(S)-THD. Absolute configurations were assigned by the chiral exciton coupling of the bis-p-(dimethylamino)benzoate of 7MBAC-3(R),4(R)-THD, and by the semiempirical methods based on the biaryl chromophores of the enantiomers of 7MBAC-5,6-DHD and of the methanolysis products of the 5,6-oxide of 7MBAC which were resolved as their (+)-HCA esters. X-ray crystallography was used for 7MBAC-8(S),9(S)-DHD bis-(+)-HCA ester, and assignments were correlated with chiral exciton coupling of the bis-4-(dimethylamino)cinnamates of 7MBAC-5(R),6(R)-DHD and 7MBAC-8(S),9(S)-DHD. The stereochemical compositions of four metabolites (three dihydrodiols and 7MBAC-5,6-oxide) formed in incubations with rat liver microsomes from control and induced liver were determined by normal-phase separations of bis-(+)-HCA esters, and by chiral stationary-phase separation of the 5,6-oxide methanolysis products. The 3(R),4(R)-enantiomer of 7MBAC-3,4-dihydrodiol predominated, 74-98% enantiomeric purity, and purity for the oxide varied from about 71% 5(R),6(S)-oxide for control microsomes to about 28% 5(R),6(S)-oxide for liver microsomes obtained from 3-methylcholanthrene-pretreated rats.

Acridines↗
PubMed1978

The effects of acridine orange on deoxyribonucleic acid in Escherichia coli.

1. Acridine Orange inhibits growth of Escherichia coli K12 when incubated at pH 7.9, but not at pH 7.4.2. At a non-permissive temperature for DNA polymerase I, Acridine Orange inhibits growth of a temperature-sensitive strain and also increases the rate of elimination of the F'-Lac plasmid. 3. DNA isolated from cells treated with Acridine Orange under conditions that inhibit growth contains material of low molecular weight, which is absent from DNA isolated from cells treated under conditions in which growth is not impaired. 4. Cells incubated with Acridine Orange at both pH 7.4 and 7.9 suffer degradation of DNA, as shown by loss of labelled DNA from the acid-insoluble fraction, which is not observed with untreated cells at either pH. 5. The results suggest that elimination of the F'-Lac plasmid by Acridine Orange requires inactivation of repair processes.

Acridines↗
PubMed1975

The influence of acridine dyes and caffeine on recovery from ultraviolet damage in Eudorina elegans.

Caffeine and the acridine dyes, acridine orange and acriflavine, were used to examine the repair potential in Eudorina elegans following ultraviolet irradiation. Acridines blocked photoreactivation primarily as a result of absorption of photoreactivating wavelengths, but acridines did not influence dark survival. Therefore, an acridine-sensitive excision-resynthesis-repair process is absent in Eudorina. Caffeine decreased both dark and light survival, the latter only after relatively high doses of ultraviolet light were used for inactivation. The caffeine-sensitive repair process appears to function most actively when the organisms are engaged in DNA synthesis, indicating that a postreplication-repair system exists in Eudorina. However, the data suggest that a repair system not associated with the DNA synthetic phases may also exist.

Acridines↗
PubMed1991

Comparison of acridine orange stain with culture and gram stain of needle aspirate in experimental Pseudomonas pneumonia.

The sensitivity and specificity of culture, acridine orange stain, and Gram stain were determined using needle aspiration (NA) material obtained from 82 rats with acute Pseudomonas aeruginosa pneumonia and 18 control rats. Lungs were then processed for either bacterial quantitation or histopathologic examination. NA culture proved to be the most sensitive and specific (55 and 100%, respectively). Sensitivity of acridine orange stain was 40%, whereas Gram stain was only 29%. The specificity of each stain was at least 94%. Lung bacterial concentrations influenced the sensitivities of all three techniques, with better sensitivity found in NA samples obtained from lung with bacterial concentration of at least 10(4) colony-forming units (cfu) of P. aeruginosa. Acridine orange and Gram stain results were similar except in NA samples from lung with bacterial concentration of less than 10(4) cfu in which acridine orange stain was more sensitive. The presence of stains identifying bacteria collected from animals with sterile NA culture was found in a small but significant number of samples, suggesting the presence of nonviable though stainable organisms. Use of all three techniques (culture, acridine orange stain, and Gram stain) increased sensitivity to approximately 70% with minimal decrease of specificity.

Acridine Orange↗
PubMed1978

Formation of free radicals from carcinogenic benz[c]acridines in the presence of proteins.

Formation of a free radical from carcinogenic and noncarcinogenic benz[c]acridine derivatives in the presence of proteins was examined. When aqueous mixture of benz[c]acridine and protein was stirred for a long period, shielded from light, benz[c]acridines were converted into free radicals. Albumin had the greatest effect in accelerating the free radical formation, and the effect was smaller in globulin, histone, and deoxyribonuclease. The g-value of the free radicals thus obtained was 2.005. Intensity of the electron spin resonance (ESR) signals of the free radical from carcinogenic derivatives was higher than those of the free radical from noncarcinogenic derivatives. There was a corresponding correlation among the ESR signal intensity of the free radical formed from the mixed system of benz[c]acridine and protein, charge of the K-region or ring nitrogen of the compound, and carcinogenicity of benz[c]acridines.

Acridines↗
PubMed1992

Comparison of the blood-brain barrier and liver penetration of acridine antitumor drugs.

The blood-brain barrier penetration of amsacrine and its analogs 9-([2-methoxy-4-[(methylsulfonyl)-amino]phenyl]amino)-,5-dimethyl- 4-acridine carboxamide (CI-921) and M-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (AC) was measured in the barbiturate-anesthetized mouse. After intracarotid administration, AC was almost completely extracted (90%) in a single transit through the brain capillaries, whereas CI-921 (20%) and amsacrine (15%) were moderately extracted. AC is retained in the brain; no loss of AC from the brain was apparent at 1, 2, 4, or 8 min after injection. In contrast, after intraportal administration, 75% of the AC, 94% of the CI-921, and 57% of the amsacrine was extracted in a single transit through the hepatic vasculature. Rather than being retained in the mouse liver, these acridine antitumor agents show time-dependent loss (t1/2 = 10 min for amsacrine and AC, 24 min for CI-921). We conclude that unlike most antitumor agents, these acridine drugs appear to penetrate the blood-brain barrier readily.

Acridines↗