Antimutagenic activity of fluphenazine in short-term tests.

Fluphenazine, an antipsychotic drug that belongs to the phenothiazine family, reduced the genotoxicity of direct- and indirect-acting mutagens in the Ames test, both in the presence and in the absence of promutagen-activating S9 fraction. In short-term tests on human lymphocytes, the inhibitory effect of fluphenazine on the genotoxicity of standard mutagens was strongest in the cytokinesis-blocked micronucleus assay and in the thioguanine resistance test, and weakest in the sister chromatid exchange test. Fluphenazine also considerably reduced the level of free radicals estimated in in vitro samples of human granulocytes. The results suggest that, in the range of the tested concentrations, fluphenazine could be considered for use to prevent the genotoxicity of daunorubicin, methyl methanesulfonate, benzo[a]pyrene, and mitomycin C. Reduction in the level of free radicals appears to be an important mechanism of the antimutagenic action of fluphenazine.

Evaluation of genotoxic and immunotoxic activities of potential glucose biosensor components: ferrocenes.

Three ferrocenes used in glucose biosensor construction were tested in the aspect of genotoxic and immunotoxic activities. All three ferrocenes were not mutagenic in the standard bacterial Ames test. Equally in the Sister Chromatid Exchanges test in human lymphocyte cultures, the genotoxic action of tested ferrocenes could be excluded. However, all three significantly decreased the rate of lymphocyte proliferation and especially diminished the numbers of B-lymphocytes and NK-cells after 72 hours of in vitro culture. Marked differences between the ferrocenes in their immunotoxic activities were noticed, and we were able to select those which would be relatively safe and those which should be avoided in further investigation of the glucose biosensor construction. Our results indicate the necessity to estimate immunotoxic effects as well as genotoxic effects, especially in biosensor components potentially used in vivo.

Inhibition of potassium dichromate mutagenicity by todralazine.

Todralazine, an antihypertensive drug of the hydrazinoph-thalazine group, markedly decreased the mutagenic activity of potassium dichromate in standard bacterial tests. At the highest todralazine dose tested inhibition of potassium dichromate mutagenic activity by approximately 90% in the Ames test and up to 100% (complete) inhibition in the Bacillus subtilis rec- assay was observed. Spectrophotometric analyses proved that todralazine induced reduction of Cr(VI) to Cr(III) and complexation of Cr(III) ions. These spectro-photometric results may be a presumptive explanation of the observed mutagenic activity decrease, as it is known that Cr(III) is poorly transported across cell membranes and therefore is not mutagenic to bacterial cells. We perceive our experiments as an example of attempts which should lead to an effective reduction in chromium genotoxic and carcinogenic activity in exposed individuals.

Antimutagenic activity of anthocyanins isolated from Aronia melanocarpa fruits.

Anthocyanins belong to the flavonoid family and are ubiquitous in plants, especially in flower petals and fruit peels. We established that anthocyanins isolated from fruits of Aronia melanocarpa markedly inhibited the mutagenic activity of benzo(a)pyrene and 2-amino fluorene in the Ames test. In the Sister Chromatid Exchanges (SCEs) test with human blood-derived lymphocytes cultured in vitro, a significant decrease of SCEs frequency induced by benzo(a)pyrene was observed in the presence of anthocyanins. In the case of mitomycin C the effect of anthocyanins on SCEs frequency was smaller but still noticeable. Anthocyanins markedly inhibited the generation and release of superoxide radicals by human granulocytes. The results suggest that the antimutagenic influence of anthocyanins is exerted mainly by their free-radicals scavenging action as well as by the inhibition of enzymes activating promutagens and converting mutagens to the DNA-reacting derivatives. These preliminary data seem to be important in the aspect of a possible antimutagenic and anticarcinogenic potency of anthocyanins commonly present in fruits and vegetables.

Antimutagenic activity of alkylresorcinols from cereal grains.

Alkylresorcinols, natural amphiphilic compounds commonly found in cereal grains, markedly decreased mutagenic activity of four standard mutagens examined in the Ames test. The effect was the strongest in the case of indirect-acting mutagens, benzo[a]pyrene and 2-aminofluorene. In the case of direct-acting mutagens, daunorubicin and methyl methanesulfonate, the diminution of the mutagenic activity by the alkylresorcinols was smaller but still noticeable. In the Sister Chromatid Exchanges test (SCEs) with cultured in vitro human blood-derived lymphocytes, a significant decrease of SCEs frequency induced by benzo[a]pyrene was observed in the presence of alkylresorcinols. These preliminary results seem to be important in the aspect of possible antimutagenic and anticarcinogenic potency of alkylresorcinols found in cereal grains.

Evaluation of the mechanisms of todralazine effect on mutagenicity of benzo(a)pyrene.

We have previously described that todralazine markedly decreased mutagenicity of several indirect- and direct-acting mutagens. In this paper we report the results of experiments conducted in order to evaluate the involvement of desmutagenic and bio-antimutagenic activities in the observed antimutagenic effect of todralazine. The results of the Ames test suggest a bio-antimutagenic, and not desmutagenic effect of todralazine. The separation of B(a)P and their derivatives by thin layer chromatography, performed after in vitro incubation of this promutagen with S9 fraction and todralazine revealed almost complete decline of B(a)P derived products in the presence of todralazine. The results indicate that the observed antimutagenic effect of todralazine on B(a)P mutagenicity is bio-antimutagenic rather than desmutagenic in their nature.

Todralazine influence upon the mutagenicity of some direct- and indirect-acting mutagens.

Todralazine decreased the mutagenic activity of tested direct- and indirect-acting mutagens. Despite the marked differences between efficient todralazine doses (ED50) it was observed that, in the case of tested indirect mutagens as well as in some of the direct mutagens, the decrease of mutagenicity by todralazine was very strong, exceeding 80% in some cases.

In vitro studies on the DNA impairments induced by Cr(III) complexes with cellular reductants.

The influence of Cr(III) complexes with ascorbic acid, cysteine and glutathione on DNA has been studied spectrophotometrically and chromatographically. The toxic and genotoxic activities of these complexes were also investigated. It was found that these complexes bind to DNA weaker than hexaaqua Cr(III) complexes. It could be explained through the greater strength of the bi- and tridentate ligands coordinated to chromium in comparison to water molecules. The formation of DNA-DNA intermolecular bonds and DNA interstrand cross-linking has been also observed. These complexes were found to be non-toxic and non-genotoxic in the bacterial test.

Study of the mechanism of todralazine antimutagenic activity: the effect upon mutagenicity of daunorubicine.

Todralazine markedly reduced the mutagenic activity of the standard direct-acting mutagen--daunorobicine (DRC)--in the Ames test. Spectrophotometric measurements proved that todralazine did not interact with DRC in water solution. Todralazine neither interacted with calf thymus DNS in vitro, nor changed the interaction of DRC with DNA. Therefore we concluded that the decrease of DRC mutagenicity observed in the Ames test should be explained rather in terms of a bioantimutagenic than a desmutagenic activity of todralazine.

Mutagenicity of B(a)P in the presence of some hydralazine derivatives.

Hydralazine, dihydralazine and todralazine were tested in the aspect of their mutagenic potency, and the influence upon the mutagenicity of standard promutagen--B(a)P. Hydralazine exhibited strong mutagenic activity in the Ames test while mutagenic activity of dihydralazine was relatively weak. Todralazine had no mutagenic activity, and significantly decreased mutagenicity of B(a)P. It was concluded that todralazine could be a good antimutagenic substance.

Mutagenic activity of drinking water in Wroclaw, Poland.

The Salmonella mutagenicity test was applied to the evaluation of mutagenic activity of Wroclaw drinking water. Contaminants of water samples were concentrated by adsorption on XAD-2 resin. After while they were eluted sequentially with acetone, dichloromethane/methanol (1:1, v/v) and methanol, and then obtained organic extracts were evaporated to dryness. The extracts were then dissolved in DMSO and examined by using the Ames test. The results proved significant contamination of drinking water with mutagenic substances. Hydroxyapatite column chromatography performed after direct incubation of standard DNA probes with tested water extracts showed that drinking water was contaminated with DNA interstrand cross-linking substances. Filtration of tap water through carbon filters markedly reduced mutagenic activity of tested water extracts, whereas ceramic filters were more efficient in depleting of DNA interstrand cross-linking contaminants.

Mutagenic activity of copper(II) chromate and dichromate complexes with polypyridines.

Copper(II) chromate and dichromate complexes with 2,2'-bipyridyl and 1,10-phenathroline were tested for their mutagenic activity in the standard Ames test. All of six tested complexes exhibited markedly lower mutagenic activity than the reference compounds--potassium dichromate and sodium chromate. The blockage of Cr(VI) reduction capability in the presence of the complex Cu2+ ion and the competition between copper and chromium ions in the interaction with cellular components are discussed in the light of the results of our previous chemical study.

Chrysotile A affects YAC-1 cytolytic activity of spleen cells.

Effect of short exposure of C57Bl/6 and F1/NZB x C57Bl/6/ mice to i.p. injected chrysotile A on YAC-1 cytolytic potential (NK cell function) of spleen cells was investigated. It was found that 3 days after injection, cytolytic activity of spleen cells was significantly abrogated and this was paralleled with an increase of alpha-naphtyl acetate esterase positive cells/macrophages in spleen cell population. In addition, effect of exposure of mice to i.p. injected chrysotile A coated with benzo(a)pyrene (BaP) was investigated. BaP did not modify the abrogative effect of chrysotile A on NK cell function. Asbestos fibres themselves were sufficient for depletion of NK cell function of spleen cells.

Genotoxicity of air pollution in a non-ferrous metal foundry in three bacterial tests and a micronucleus test--a comparative study.

Acetone extracts of dusts and fumes collected at workplaces in a non-ferrous metal foundry exhibited genotoxic activity in all of the tests used. Of the compared tests, the Ames method is the most useful for preliminary screening detection of the genotoxic agents that are present in acetone extracts of dusts and fumes emitted at workplaces in a non-ferrous metal foundry.

Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test.

The potential effect of asbestos fibers on mutagenicity of benzo(a)pyrene was investigated by using the Ames test. Asbestos fibers without a coating of benzo(a)pyrene or benzo(a)pyrene when not dissolved in DMSO lacked any mutagenic effect in the Salmonella/mammalian microsome mutagenicity test. However, when benzo(a)pyrene was adsorbed onto asbestos, significant numbers of mutated bacteria were observed. This shows that asbestos fibers can serve a carrier role presenting benzo(a)pyrene to the enzymatic microsomal system, thus enhancing mutagenicity of this compound.

Polynucleotide sequence divergence among some coagulase-negative staphylococci.

The degree of binding was determined, at both exacting and non-exacting temperatures, between deoxyribonucleic acid (DNA) preparations from coagulase-negative staphylococci and carbon (14C) labelled DNA from nine reference strains, Staphylococcus capitis LK499, S. cohnii GH137, S. epidermidis GH37, S. haemolyticus SM131, S. hominis DM122, S. saprophyticus CCM883, S. simulans SM128, S. warneri AW25 and S. xylosus KL162. The close similarity in nucleotide sequences found between five of the six representatives received as S. capitis, S. hominis and S. warneri indicate that these organisms are separated into too many species. In contrast, little homology was found between the pairs of strains representing S. cohnii and S. haemolyticus, respectively. The divergence indices of the nine reference strains were calculated and the relationship between them expressed in a sorted similarity matrix and dendrogram based upon the average linkage algorithm. The pattern of nucleotide heterogeneity was found by plotting the relative DNA bound at the exacting temperature against the divergence indices. The coagulase-negative staphylococci exhibit extensive genetic diversity due mainly to random mutation.

DNA homology studies on Nocardia and Rhodococcus strains.

The genetic homogeneity of Nocardia amarae, Nocardia autotrophica and Rhodococcus strains and the relationship among these groups of microorganisms have been studied using the DNA reassociation method. Strains belonging to N. amarae and N. autotrophica form genetically homogeneous groups. Distinct differences have been found out among Rhodococcus strains.

Deoxyribonucleic acid reassociation in the classification of the 'rhodochrous' complex and allied taxa.

The degree of binding was determined between DNA preparations from gordonae and rhodochrous strains and uracil-labelled DNA from five reference strains, Nocardia asteroides NK20, N. pellegrino PII, Gordona bronchialis TI, G. terrae T5 and rhodochrous strain R90. Most of the rhodochrous and pellegrino strains fell into one of two genetically homogeneous taxa. The nucleotide sequence homology data also suggested that G. bronchialis, G. rubra, and more equivocally G. terrae, formed distinct species. However, the values for DNA relatedness between these species, and between then and the rhodochrous homology groups, were comparatively low. Only a small degree of nucleotide sequence homology was found between the N. asteroides reference system and the rest of the taxa studied. The nucleotide composition of the DNA preparations from 29 of the 30 test strains fell between 63 and 69 mol% guanine plus cytosine.