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Biomedical subjects

K Gasiorowski

Publications and source records attributed to K Gasiorowski.

At least 19 recordsLinked to original sources
PubMed2001

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.

Adult↗
PubMed2001

A comparison of the methods applied to detect apoptosis in genotoxically-damaged lymphocytes cultured in the presence of four antimutagens.

The sensitivity of the available methods of apoptosis detection in lymphocyte cultures was tested. Cells were preincubated with genotoxic agents: hydrogen peroxide (0.2 mM; 20 min.) and benzo[a]pyrene (40 microM; 90min.), and then cultured for 36h in the presence of a lectin (PHA-M; 1% v/v) and one of the following potentially antimutagenic agents: alkylresorcinols, anthocyanins, todralazine and fluphenazine. It was established that staining with a mixture of fluorochromes (ethidium bromide and acridine orange) provided the highest amount of detected apoptotic cells, and the best repeatability of the results in subsequent experiments. Calculation of the Spearman's rank correlation coefficients proved that there was a high correlation between the results obtained by the ethidium bromide/acridine orange method and those obtained by identifying genomic DNA fragmentation by means of FIGE-electrophoresis. Therefore, these two methods were chosen for further studies of the tested antimutagens' impact on apoptosis in genotoxically-damaged lymphocytes.

Acridine Orange↗
PubMed2001

Impact of four antimutagens on apoptosis in genotoxically damaged lymphocytes in vitro.

An antimutagenic activity of fluphenazine, todralazine, anthocyanins and alkylresorcinols was established in a battery of short-term cytogenetic tests. One of the possible mechanisms of their antimutagenic action could be an increase in apoptotic elimination of heavily-damaged cells from a culture. In this paper we provide data on quantitative estimation of the antimutagens' impact on apoptosis in lymphocyte cultures exposed in the G(0)-phase to genotoxic agents: hydrogen peroxide (0.2mM, 20 min.) or benzo[a]pyrene (40 microM, 90 min.), and then cultured for 36 hrs in the presence of a lectin (PHA-M, 1% v/v) and each of the tested antimutagens. Apoptosis was estimated by means of microscopic examination of cell smears stained with a mixture of fluorochromes (ethidium bromide/acridine orange) as well as of the results of DNA separation with the field inversion gel electrophoresis. By microscopic examination we assessed that the frequencies of cells exhibiting morphological features of apoptosis considerably increased in the cultures containing the antimutagens. The FIGE separation of DNA from those cultures proved that the DNA content in the 30-50 kb domain was markedly elevated, as compared with the control cultures that did not contain antimutagens. It was established in the regression analysis that the apoptosis-enhancing effect significantly depended on the concentration of each tested antimutagen in a culture medium. However, marked differences of apoptosis-enhancing potency were noticed among the four antimutagens. The multicriterial analysis proved that the apoptosis-enhancing effects of fluphenazine and also, to a smaller extent, by alkylresorcinols, were many times stronger than those of anthocyanins and of todralazine. The results suggest that the enhancement of apoptosis by fluphenazine and by alkylresorcinols can explain a major part of their antimutagenic activity, whereas in the case of anthocyanins and of todralazine other mechanisms of antimutagenic action should be sought for.

Antimutagenic Agents↗
PubMed2001

DNA repair of hydrogen peroxide-induced damage in human lymphocytes in the presence of four antimutagens. A study with alkaline single cell gel electrophoresis (comet assay).

We assessed four antimutagenic compounds' influences on DNA repair in human lymphocytes exposed in vitro to hydrogen peroxide (20 microM, 5 min, at 4 degrees C). DNA damage and repair were estimated by means of alkaline single cell gel electrophoresis (comet assay). It was noticed that the enhancement of DNA repair was relatively strongest when fluphenazine was present in the cell culture medium. In the cases of anthocyanins and alkylresorcinols, the effects were almost 6-9 times weaker than that of FPh. The effect of todralazine on DNA repair was relatively weakest. Further study should be done on fluphenazine as a potential DNA repair-enhancing compound.

Adult↗
PubMed2000

Evaluation of antimutagenic effect of todralazine in cultured lymphocytes.

Todralazine, an antihypertensive drug from the hydrazinophthalazine group, significantly decreased the activities of benzo[a]pyrene and mitomycin C in three short-term genotoxicity tests in human lymphocyte cultures. The thioguanine resistance test, the cytokinesis-blocked micronucleus assay and the sister chromatid exchange test were used to demonstrate the antimutagenicity of todralazine. Todralazine lowered the level of free radicals generated by human granulocytes in vitro in the presence of benzo[a] pyrene and also in the presence of the granulocyte activator and tumor promoter phorbol myristate acetate. These results, together with our previous data obtained in the standard bacterial Ames test, strongly suggest that todralazine is a good antimutagen in vitro and deserves further research on its inhibitory action on mutagenesis and carcinogenesis.

Adult↗
PubMed1999

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.

Biosensing Techniques↗
PubMed1997

A proposed new strategy of immunotherapy for Alzheimer's disease.

Current data on the involvement of the immunological system in the pathogenesis of Alzheimer's disease (AD) are discussed, and results of immunotherapy for the disease are provided. Hypotheses on immune aging as a risk factor for AD, and a suggested new treatment strategy, are presented and discussed.

Aging↗
PubMed1997

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.

Antihypertensive Agents↗
PubMed1996

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.

Antimutagenic Agents↗
PubMed1995

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.

Animals↗
PubMed1994

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.

4-Nitroquinoline-1-oxide↗
PubMed1994

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.

Animals↗
PubMed1993

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.

Antimutagenic Agents↗
PubMed1993

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.

Animals↗
PubMed1993

Alzheimer's disease--immunological aspects.

Alzheimer's Disease (A.D.) is a multifarious, complex syndrome, which probably comprises different etiopathogenic subunits. Work by several authors has shown immunological disturbances in A.D. underlining the importance of immunological imbalance in the explanation of the etiopathogenesis and progress of some forms of A.D. An early diagnosis of A.D. is important because changes in central nervous system respond well to immunomodulatory treatment in the early course of disease. This justifies a search for diagnostic methods permitting an early diagnosis of the disease and establishment of immunological disturbances and consequently an early start of treatment. In the present paper, the literature regarding immunological disturbances observed in A.D. patients is reviewed.

Alzheimer Disease↗
PubMed1992

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.

2,2'-Dipyridyl↗
PubMed1990

Influence of dihydralazine on the generation of hydroxyl radicals by human granulocytes.

Hydroxyl radical generation by living human granulocytes was determined by ESR using DMPO as a spin trapping reagent. The influence of dihydralazine and exogenous superoxide dismutase (SOD) on the radical generation was observed. In the presence of dihydralazine the radical production increases distinctly; the higher hydroxyl radical production is observed for the dihydralazine-SOD containing system which is explained by the partial decomposition of the enzyme in the presence of dihydralazine. No effect of dihydralazine on the lipid fluidity of the granulocyte membrane and phase transition in the membrane of living granulocytes was observed.

Cell Membrane↗