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Biomedical subjects

L Novotný

Publications and source records attributed to L Novotný.

At least 37 records · Page 2Linked to original sources
PubMed1998

Staurosporine enhanced benzamide riboside-induced apoptosis in human multidrug-resistant promyelocytic leukemia cells (HL-60/VCR) in vitro.

The inosine monophosphate (IMP) dehydrogenase inhibitor benzamide riboside (BR) induced apoptosis (detected with the aid of flow cytometric identification of cells with sub-G0 DNA content and increased side angle light scatter) equally or slightly more intensively in the multidrug-resistant human promyelocytic leukemia cell line (HL-60/VCR: MDR-1 gene, Pgp positive) in comparison with the parental drug sensitive HL-60 cells. Staurosporine alone induced relatively low level of apoptosis in parental HL-60 cells but higher level (approximately 35%) of apoptosis in multidrug-resistant HL-60/VCR cells after 24 hour induction. The combination of benzamide riboside and staurosporine induced in both drug-sensitive and drug-resistant HL-60 cells a marked proportion of apoptotic cells already after short (6 hour) induction (more than 30% of apoptotic cells).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Evaluation of potential carcinogenicity of steroidal alkaloids from Veratrum album L. by the DC polarography method.

The presented work is devoted to the study of polarographic reduction in the series of 13 alkaloids isolated from various parts of Veratrum album subsp. lobelianum. The used compounds were evaluated from the point of view of their potential carcinogenicity in anhydrous N,N-dimethylformamide (DMF) by the method of DC polarography. All compounds were reduced during an one two-electron irreversible step. Their potential carcinogenicity characterized by a parameter tg alpha value determined in the presence of alpha-lipoic acid ranged from the highest value 0.257 obtained for the solanidane skeleton containing rubijervine to the value 0.070 for jervine. The tg alpha value determined for rubijervine (0.257) is comparable with the tg alpha of naphto-(2',1',2,3)fluoranthene (0.270)-compound classified by IARC as possible carcinogen for human. The tg alpha values determined for other alkaloids were relatively low and they do not indicate any possible carcinogenic activity.

Alkaloids↗
PubMed1998

Macrocyclic Cu(II)tetraanhydroaminobenzaldehyde complex--antiproliferative activity in vitro and in vivo.

The macrocyclic Cu(II)-tetraanhydroaminobenzaldehyde complex Cu(TAAB)C12 induces various cytotoxic effects in the dependence on a cell line, concentration and time of exposition. The highest complex concentration of 914 nmol/l induces degeneration of certain part of the HeLa cells population after 24 hours of cultivation. The concentration of 183 nmol/l causes a delayed cytotoxic effect on HeLa and HepG2 cells. After 24 hours of culturing 15.4-28.4% of cell population proliferated but after 48 and 72 hours 2.0-42.3% of the cell population degenerated. The cytotoxic effect on V79 cells is directly dependent on the actual concentration and time of the complex influence. The cytotoxic concentrations of Cu(TAAB)Cl2 induce an integrity damage of cytoplasmatic membrane and two phase unbalanced growth. Cu(TAAB)Cl2 possesses an antileukemic activity which at the dose of 10 mg/kg of body weight is not accompanied by side toxic effects on mice.

Animals↗
PubMed1998

Pentoxifylline stimulates drug-induced apoptosis in leukemic cells.

Camptothecin (CAM) and cisplatin (cis-diamminedichloroplatinum(II), cis-Pt) were used as inducers of apoptosis in the mouse leukemic L1210 cells. Relatively high concentrations of 50 micromol cis-Pt and 50 micromol CAM, respectively, were used to induce the apoptotic DNA ladder. The simultaneous treatment of L1210 cells by the drug and pentoxifylline (PTX) resulted in a decrease of drug concentrations necessary for the induction of apoptosis. This study revealed that a cell cycle G2 checkpoint inhibitor PTX reduces time intervals necessary for the onset of drug-induced apoptosis in these cells. This fact might be important as the earlier onset of programmed cell death may decrease a risk of tumor cells to become resistant to drug therapy.

Animals↗
PubMed1997

Simultaneous determination of the new anticancer agent amidox and its metabolites in rat bile and plasma by high-performance liquid chromatography.

A new reversed-phase ion-pair high-performance liquid chromatography method was developed to study the first-pass hepatic metabolism of the anti cancer drug amidox in bile. Separation of the metabolites was achieved on a Spherisorb C18 column after liquid-liquid extraction using a linear gradient system of heptanesulfonic acid in potassium phosphate monobasic (pH 4.0) with increasing amounts of methanol (0-40%). The method was further applied to a pharmacokinetic study of amidox in rats after 200 mg kg-1 intraperitoneal administration. Using 50 microliters of rat bile and 300 microliters of rat plasma the limit of detection for amidox was 60 ng and 85 ng, respectively, and the assay was linear from 0.1 to 150 micrograms ml-1. This method appears to be sensitive enough to be used in further pharmacokinetic studies of amidox in human volunteers.

Animals↗
PubMed1997

Taxol-enhanced cytotoxic effect of radiation in human promyelocytic leukemia cells: relative resistance of multidrug-resistant HL-60 cells in vitro.

Cytotoxic effects of sequential taxol (paclitaxel) and X-irradiation on drug-sensitive human cultured promyelocytic leukemia (HL-60) cell line and its multidrug-resistant sublines were examined using photometric MTT test and flow cytometry. Paclitaxel (at concentrations 1-10 nmol) stimulated the cytotoxic effect of irradiation in HL-60 and to a lesser extent also in HL-60/ADR, but not in HL-60/VCR cells. The stimulation of radiation-induced cytotoxic effect by paclitaxel correlated with its potential to induce cell cycle and viability alterations identified with flow cytometric analysis (i.e. increased propidium iodide staining, increased side scatter, decreased forward angle scatter, accumulation of necrotic cell detritus, apoptotic pre-G0 cells and cells in the G2/M phase of the cell cycle).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Polarographic testing of carcinogenicity of some chemotherapeutics.

This work is devoted to the study of polarographic reduction of three antibiotic compounds including adriamycin, chloramphenicol and erythromycin and of a synthetic antibacterial chemotherapeutic compound--5-nitrofurantoin. The polarographic reduction was performed in the strictly anhydrous N,N-dimethylformamide with or without alpha-lipoic acid (LA) by the means of DC polarography. The values of half-wave potentials E1/2 and parameter of potential carcinogenicity were determined for the all compounds. Adriamycin was reduced during the five-step process, other compounds were reduced in two steps. The presence of LA in a polarographic solution resulted in a new polarographic one-electron wave in the range of -1.120 V to -1.790 V vs. SCE possessing a diffuse and reversible character. Its height is linearly dependent on the LA concentration in solution. The highest parameter of potential carcinogenicity tg alpha was determined for adriamycin (0.575) which belongs among compounds classified by WHO as "probably carcinogenic to humans". The lowest determined value of parameter tg alpha belonged to 5-nitrofurantoin (0.290) which has not yet been included into the IARC classification.

Anti-Bacterial Agents↗
PubMed1996

Chromatographic properties of cytosine, cytidine and their synthetic analogues.

A direct reversed-phase high-performance liquid chromatographic (RP-HPLC) assay was used for the study of the effects of methanol concentration, pH, flow-rate of the mobile phase and column temperature on the retention of the natural nuclei acid components cytosine and cytidine and their synthetic 1-beta-D-arabinofuranosyl, 5-aza and 6-aza analogues. The pKa values were also determined. The greatest changes were observed with changes in pH. The relationship between the capacity factors and the hydrophobicity of the compounds studied was also investigated.

Chromatography, High Pressure Liquid↗
PubMed1996

Polarographic reduction of some triphenylmethane dyes and their potential carcinogenic activity.

Polarographic reduction of some triphenylmethane dyes in strictly anhydrous solutions was studied in the absence and presence of alpha-lipoic acid. The values of the half-wave potentials E1/2 and the parameter of potential carcinogenicity tg alpha were determined for all compounds studied. The current value of the first diffuse polarographic wave was increased in the presence of alpha-lipoic acid for all of the compounds. The increase was linear and depended on the alpha-lipoic acid concentration in anhydrous solutions. The highest determined value of tg alpha belonged to crystal violet (0.420) and to methyl violet 2B (0.440). The values indicate potential carcinogenic activities of the respective triphenylmethane dyes.

Carcinogens↗
PubMed1996

Polarographic behavior of kojic acid and its derivatives, determination of potential carcinogenicity and correlation of these properties with their other attributes.

Polarographic properties of kojic acid [5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one] and 10 of their synthetic derivatives were investigated. It was shown that these compounds are reduced in anhydrous conditions, usually in one two-electron step or in two one-electron steps. The presence of some substituents may change the course of reduction process. The polarography of these compounds in the presence of alpha-lipoic acid showed the kojic acid analog-alpha-lipoic acid complex formation. The determined potential carcinogenic activity of these compounds expressed as a parameter tg alpha is not substantial.

Carcinogenicity Tests↗
PubMed1996

Potential carcinogenicity of the synthetic 1,3,6-triazine (6-aza) nucleic acid analogues determined by DC polarography. I. Nucleobases.

The polarographic reduction of several synthetic 1,3,6-triazine (6-aza) nucleobases in the strictly anhydrous solution was studied in the absence and presence of alpha-lipoic acid. The values of the half-wave potentials E1/2 and the parameter of potential carcinogenicity tg alpha were determined for one natural and 5 synthetic nucleobases. The current value of the first diffuse polarographic wave or a new diffuse polarographic wave belonging to the nucleobase-alpha-lipoic acid complex increased with the increased alpha-lipoic acid concentration for the all compounds only marginally. Although this diffuse current increase was linearly depended on the alpha-lipoic acid concentration in anhydrous solutions, the determined index tg alpha values ranging between 0.029 and 0.108 indicated a very low potential carcinogenicity of the all nucleobases investigated.

Aza Compounds↗
PubMed1995

The disposition of new arabinosylcytosine derivative-- 5'-chloro-5'-deoxy-arabinosylcytosine--in rats.

1. Pharmacokinetic properties of a new derivative of the widely used and very potent antileukemic agent arabinosylcytosine (araC)--5'chloro-5'-deoxy-arabinosylcytosine (5'-Cl-araC)--were investigated after intraperitoneal (i.p.) and oral routes of administration in rats and compared with the equimolar dose of araC administered orally. 2. It was found that substitution of the hydroxyl group at position 5' resulted in a change of pharmacokinetic parameters. 3. There is a large difference in average serum concentrations of 5'-Cl-araC administered by the i.p. and oral routes; the average serum concentration obtained after i.p. injection being several times higher in comparison to those after oral administration. 4. However, the latter are, at the same time, lower than the average serum concentrations of araC administered by the same route in an equimolar dose. 5. On the other hand, the apparent volume of distribution is much larger, and the area under the curve of serum concentration of 5'-Cl-araC is smaller, after oral as compared to the i.p. route of administration indicating more extensive tissue distribution together with higher tissue binding of 5'-Cl-araC when compared to the parental drug araC.

Administration, Oral↗
PubMed1995

Antileukemic activity of 4-pyranone derivatives.

In a search for new compounds possessing antitumor activity, we examined the effects of a group of oxygen containing heterocyclic derivatives on L1210 murine leukemia cell growth. Several 5-hydroxy-2-hydroxymethyl-4-pyranone derivatives were tested in a growth assay employing a human leukemia K562 cells line. IC50 was extrapolated from the growth inhibition curves at compound concentrations ranging from 0.1 to 100 microM. The halogen derivatives of 5-hydroxy-2-hydroxymethyl-4-pyranone inhibited L1210 cell growth in suspension culture after 96 hr incubation in the following order: 5-hydroxy-2-iodomethyl-4-pyranone (IC50 3.15 microM) > 6-bromo-2-bromomethyl-5-hydroxy-4-pyranone (IC50 3.40 microM) > 6-bromo-5-hydroxy-2-hydroxy-methyl-4-pyranone (IC50 3.75 microM) > 2-bromomethyl-5-hydroxy-4-pyranone (IC50 4.30 microM) > 5-benzyloxy-2-chloromethyl-4-pyranone (IC50 5 microM) > 6-bromo-2-chloromethyl-4-pyranone (IC50 13.50 microM) > 6-chloro-2-chloromethyl-5-hydroxy-4-pyranone (IC50 18 microM) > 2-chloromethyl-5-hydroxy-4-pyranone (IC50 20 microM). The compound, 5-hydroxy-2-hydroxymethyl-4-pyranone has no effect on L1210 cell growth. These results suggest that 5-hydroxy-2-hydroxymethyl-4-pyranone derivatives might represent a new class of compounds with antileukemic activity.

Animals↗
PubMed1995

Potential carcinogenicity of homoisoflavanoids and flavonoids from Resina sanguinis draconis (Dracaena cinnabari Balf.).

Polarographic behavior of three homoisoflavanoids and four flavanoids isolated from the dragon's blood (Resina sanguinis draconis. Dracaena cinnabari Balf.), collected at Sokotra, was investigated in aprotic solution and an index of potential carcinogenicity tg alpha was determined. Generally, homoisoflavanoids and flavanoids were reduced in two two-electron steps, the first being reversible and the second one irreversible. The parameter tg alpha values indicated that the majority of these compounds possesses no or only marginal potential carcinogenic activity. However, it was demonstrated that some structural modifications in basic flavonoid structure lead to changed electrochemical properties and a substantial increase of derivative potential carcinogenicity.

Carcinogens↗
PubMed1994

Effect of arabinosylcytosine derivative cyclocytidine on hepatal functions in rats and on Zajdela hepatoma.

1. The effectivity of the arabinosylcytosine (araC) derivative, cyclocytidine (cC), against Zajdela hepatoma was evaluated. It was established that the cC effect was dose-dependent. 2. Zajdela hepatoma-bearing rats, given a single dose of 500 mg of cC per kg of body weight, showed an increased life span of 48 and 39%. 3. cC significantly decreased the number of Zajdela hepatoma cells in ascitic fluid and affected the cytochrome content in hepatal mitochondria. 4. The overall cC effect on the hepatal function of normal and hepatectomized liver was marginal, thus making this araC derivative an interesting candidate for further evaluation of its effectivity against non-hematological tumors.

Ancitabine↗
PubMed1993

DNA breakage and inactivation resulting from hydroxylamine and/or cis-diamminedichloroplatinum(II) interactions with plasmid DNA.

1. Occurrence of lesions induced in plasmid DNA by cis-DDP and by HA was quantified both as a transforming activity and as conformation integrity of supercoiled pBR322 DNA. Fifty per cent decrease of the biological activity of plasmid DNA, not accompanied by measurable change of DNA conformation, was observed after a single exposure of DNA to cis-DDP (1 hr/37 degrees C). 2. HA induced conversion of supercoiled DNA to other topological forms in a dose-dependent manner. 3. One- and two-strand DNA breaks were determined electrophoretically with high sensitivity. Cis-DDP exposed DNA relaxed at 30 times lower HA concentration compared to intact DNA. 4. This effect may be connected with a local distortion of DNA structure at the cis-DDP--DNA bond, which makes possible high effectivity of HA-DNA interaction. 5. On other hand, biological activity stayed at the 50% level despite breaks induced in DNA. 6. This finding supports the idea that DNA breaks occur at the locations which were modified during the exposure of DNA to cis-DDP. 7. The importance of the DNA structure during interaction with HA may be seen during HA-DNA interaction at heat-denaturation of supercoiled DNA. At this condition, the DNA breaks were induced at 100 times lower concentration of HA. 8. We conclude, on the basis of these results published earlier, that local distortion of supercoiled DNA structure, which is caused by the cis-DDP bond, and the local DNA uncoiling caused by heat-denaturation are related to high HA-DNA reactivity.

Cisplatin↗
PubMed1993

Polarographic reduction and carcinogenic index tg alpha of 5-aza nucleosides possessing antileukemic activity.

Polarographic behavior of arabinosyl-5-azacytosine (ara-AC) and 5-azacytidine in anhydrous dimethylformamide and in Britton Robinson buffer is described. 5-Azacytidine and ara-AC underwent two-electron reduction under the polarographic conditions used. Carcinogenic index tg alpha estimated in the presence of alpha-lipoic acid was 0.295 for 5-azacytidine and 0.275 for ara-AC.

Antineoplastic Agents↗