Uptake of (14)C-labeled fluoranthene ([(14)C]FLT) via both roots and leaves of Pisum sativum seedlings and distribution of [(14) C] in plants by both acropetal and basipetal transport was evaluated. The highest [(14)C] level was found in the root base (≈270 × 10(4) dpm/g dry wt) and the lowest level in the stem apex (<2 × 10(4) dpm/g dry wt) after just 2 h of root exposure. For foliar uptake, the highest level of [(14)C] was found in the stem and root apex (both ≈2 × 10(4) dpm/g dry wt) (except for treated leaves), while the lowest level was found in the root base (<0.6 × 10(4) dpm/g dry wt).

• Klíčová slova
• Fate and transport, Pea plant, Phytotoxicity, Polycyclic aromatic hydrocarbons, Root and foliar uptake,
• MeSH
• biologický transport MeSH
• fluoreny analýza   metabolismus   MeSH
• hrách setý metabolismus   MeSH
• kořeny rostlin metabolismus   MeSH
• látky znečišťující životní prostředí analýza   metabolismus   MeSH
• listy rostlin metabolismus   MeSH
• monitorování životního prostředí MeSH
• radioizotopy uhlíku analýza   metabolismus   MeSH
• stonky rostlin metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fluoranthene MeSH Prohlížeč
• fluoreny MeSH
• látky znečišťující životní prostředí MeSH
• radioizotopy uhlíku MeSH

Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

• Klíčová slova
• Antimutagenic, Bilirubin, Circular dichroism, Molecular docking, Mutagens, Serum albumin,
• MeSH
• bilirubin chemie   metabolismus   MeSH
• cirkulární dichroismus MeSH
• fluoreny chemie   metabolismus   MeSH
• lidé MeSH
• mutageny chemie   metabolismus   MeSH
• sérový albumin chemie   metabolismus   MeSH
• simulace molekulového dockingu MeSH
• skot MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-aminofluorene MeSH Prohlížeč
• 2,4,7-trinitrofluorenone MeSH Prohlížeč
• 2,7-fluorenediamine MeSH Prohlížeč
• bilirubin MeSH
• fluoreny MeSH
• mutageny MeSH
• sérový albumin MeSH

Biotransformation products of two potential antineoplastic agents, benfluron and dimefluron, are characterized using our integrated approach based on the combination of high-performance liquid chromatography (HPLC) separation of phase I and phase II metabolites followed by photodiode-array UV detection and electrospray ionization tandem mass spectrometry (MS/MS). High mass accuracy measurement allows confirmation of an elemental composition and metabolic reactions according to exact mass defects. The combination of different HPLC/MS/MS scans, such as reconstructed ion current chromatograms, constant neutral loss chromatograms or exact mass filtration, helps the unambiguous detection of low abundance metabolites. The arene oxidation, N-oxidation, N-demethylation, O-demethylation, carbonyl reduction, glucuronidation and sulfation are typical mechanisms of the metabolite formation. The interpretation of their tandem mass spectra enables the distinction of demethylation position (N- vs. O-) as well as to differentiate N-oxidation from arene oxidation for both phase I and phase II metabolites. Two metabolic pathways are rather unusual for rat samples, i.e., glucosylation and double glucuronidation. The formation of metabolites that lead to a significant change in the chromophoric system of studied compounds, such as the reduction of carbonyl group in 7H-benzo[c]fluorene-7-one chromophore, is reflected in their UV spectra, which provides valuable complementary information to MS/MS data.

• MeSH
• antitumorózní látky metabolismus   moč   MeSH
• biochemické jevy MeSH
• fluoreny metabolismus   moč   MeSH
• glukosidy metabolismus   moč   MeSH
• glukuronidy metabolismus   moč   MeSH
• krysa rodu Rattus MeSH
• metabolické sítě a dráhy MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• dimefluron MeSH Prohlížeč
• fluoreny MeSH
• glukosidy MeSH
• glukuronidy MeSH
• VUFB 13468 MeSH Prohlížeč

Dissolved organic matter (DOM) in freshwaters is present at concentrations ranging from 0.5 to 50 mg L⁻¹, and consists of various organic compounds, including humic substances (HS). HS exert a variety of direct and indirect biological effects, including interaction with the aryl hydrocarbon receptor (AhR). AhR is a cytosolic receptor that binds various hydrophobic organic compounds (HOCs) and mediates some of their toxic effects. In vitro effects of binary mixtures of various DOM (mainly HS) with various HOCs on AhR-mediated responses were studied by use of H4IIE-luc cells. Six out of 12 DOM activated the AhR even at environmentally relevant concentrations (17 mg L⁻¹). In simultaneous exposures of H4IIE-luc cells to DOM (17 mg L⁻¹) and each of the model compounds, 2,3,7,8-TCDD, PCB126, PCB169, benzo[a]pyrene, benzo[a]anthracene, dibenz[a,h]anthracene, fluoranthene, a mixture of persistent organic pollutants (POPs), a mixture of polycyclic aromatic hydrocarbons (PAHs), and a mixture of all HOCs, either significant additive or facilitative effects were observed when compared to activities of single HOCs. No significant decrease of effects due to possible sorption of HOCs to DOM was observed, even in subsequent experiments when HOCs+DOM mixtures were preincubated for six days before exposure to H4IIE-luc. Thus, DOM does not seem to protect organisms against AhR-mediated toxic effects of HOCs (as usually predicted due to sorption of HOCs on DOM), but it can actually enhance their potency for AhR-mediated effects in some situations.

• MeSH
• anthraceny chemie   metabolismus   toxicita   MeSH
• benzopyren chemie   metabolismus   toxicita   MeSH
• fluoreny chemie   metabolismus   toxicita   MeSH
• huminové látky analýza   MeSH
• hydrofobní a hydrofilní interakce MeSH
• krysa rodu Rattus MeSH
• látky znečišťující životní prostředí chemie   metabolismus   toxicita   MeSH
• nádorové buněčné linie MeSH
• organické látky chemie   metabolismus   toxicita   MeSH
• polychlorované dibenzodioxiny chemie   metabolismus   toxicita   MeSH
• polycyklické aromatické uhlovodíky chemie   metabolismus   toxicita   MeSH
• receptory aromatických uhlovodíků metabolismus   MeSH
• sladká voda chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthracene MeSH Prohlížeč
• anthraceny MeSH
• benzopyren MeSH
• fluoranthene MeSH Prohlížeč
• fluoreny MeSH
• huminové látky MeSH
• látky znečišťující životní prostředí MeSH
• organické látky MeSH
• polychlorované dibenzodioxiny MeSH
• polycyklické aromatické uhlovodíky MeSH
• receptory aromatických uhlovodíků MeSH

Seventy-nine white rot strains were screened to determine if they had the potential for use in the degradation of oligocyclic aromates (PAHs) by measuring their dye-decoloration rate. Fourteen strains that were selected based on their dye-decoloration rate were then evaluated for the ability to tolerate various levels of PAHs spiked in agar medium. The ability of white rot fungi to degrade 3- or 4-ring PAHs (anthracene, phenanthrene, fluoranthene, pyrene) was determined. Two strains of Phanerochaete sordida (KUC8369, KUC8370) were possible PAHs degraders, degrading a significantly greater amount of phenanthrene and fluoranthene than the culture collection strain P. chrysosporium (a known PAHs degrader). The production of manganese peroxidase, the only extracellular ligninolytic enzyme detected during the cultivation, was evaluated.

• MeSH
• barvicí látky MeSH
• Basidiomycota klasifikace   genetika   růst a vývoj   metabolismus   MeSH
• biodegradace MeSH
• DNA fungální analýza   genetika   MeSH
• fenantreny metabolismus   MeSH
• fluoreny metabolismus   MeSH
• kultivační média MeSH
• mezerníky ribozomální DNA analýza   genetika   MeSH
• molekulární sekvence - údaje MeSH
• peroxidasy metabolismus   MeSH
• Phanerochaete klasifikace   genetika   růst a vývoj   metabolismus   MeSH
• polycyklické aromatické uhlovodíky metabolismus   MeSH
• sekvenční analýza DNA MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• barvicí látky MeSH
• DNA fungální MeSH
• fenantreny MeSH
• fluoranthene MeSH Prohlížeč
• fluoreny MeSH
• kultivační média MeSH
• manganese peroxidase MeSH Prohlížeč
• mezerníky ribozomální DNA MeSH
• peroxidasy MeSH
• phenanthrene MeSH Prohlížeč
• polycyklické aromatické uhlovodíky MeSH

In this study, the chromatographic behaviour of four mixtures of compounds was tested on columns possessing various surface properties. Cocaine, dimefluron, nabumetone, and tramadol were chosen as the test compounds. Cocaine is a tropane alkaloid, which is relatively often abused as a drug. This is why many papers have already been written about its determination in human biological samples. Dimefluron, a derivative of benzo[c]fluorene, is a new perspective drug being investigated for its potential antineoplastic effects. Nabumetone is a non-steroidal anti-inflammatory prodrug used for treatment of inflammatory and degenerative rheumatic diseases. Tramadol, derived from an opioid structure is used as an anodyne for treatment of severe pain. As a medicament it is usually determined either in biological samples or in pharmaceuticals. The above-mentioned model drugs were separated using chromatographic columns with C18, C8, palmitamidopropyl, and pentafluorophenylpropyl chains. The best conditions for separation of the individual compounds and their metabolites were chosen on the basis of resolution, retention times, and peak symmetry.

• MeSH
• analgetika analýza   chemie   metabolismus   MeSH
• antiflogistika nesteroidní analýza   chemie   metabolismus   MeSH
• antitumorózní látky analýza   chemie   metabolismus   MeSH
• butanony analýza   chemie   metabolismus   MeSH
• fluoreny analýza   chemie   metabolismus   MeSH
• kokain analýza   chemie   metabolismus   MeSH
• léčivé přípravky analýza   chemie   metabolismus   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nabumeton MeSH
• referenční standardy MeSH
• tramadol analýza   chemie   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie metody   normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• analgetika MeSH
• antiflogistika nesteroidní MeSH
• antitumorózní látky MeSH
• butanony MeSH
• dimefluron MeSH Prohlížeč
• fluoreny MeSH
• kokain MeSH
• léčivé přípravky MeSH
• nabumeton MeSH
• tramadol MeSH

The disposition of a new potential antineoplastic drug dimefluron after an oral administration to rats was investigated. Dimefluron, 3,9-dimethoxy-5-(2-dimethylaminoethoxy)-7H-benzo[c]fluoren-7-one hydrochloride, was administered in a single oral dose (250 mg kg(-1) of body weight) in the form of an aqueous solution via a gastric probe. Dimefluron metabolites were being searched for in rat faeces. Synthetic standards of the expected phase I metabolites (the products of O- and N-desmethylation, N-oxidation and carbonyl reduction of dimefluron) were prepared and used together with dimefluron and internal standard in the development of two HPLC bioanalytical methods based on different separation principles. The first separation of dimefluron and the phase I metabolites was tested on a 250 mm x 4 mm chromatographic column with LiChrospher 60 RP-selectB 5 microm (Merck) using an isocratic mobile phase containing 0.01 M nonylamine buffer (pH 7.4) and acetonitrile in the 1:2 ratio (v/v). The second separation was performed on a 250 mm x 4 mm chromatographic column Discovery HS F5, 5 microm (Supelco) using a linear gradient mode with the mobile phase containing acetonitrile and phosphate buffer (0.05 M KH2PO4, pH 3). The flow rate was 1 ml min(-1) in both cases. UV detection was performed in the dual wavelength mode, with 317 nm having been used for dimefluron and all 7H-benzo[c]fluoren-7-one metabolites, 367 nm for 7H-benzo[c]fluoren-7-ol metabolites. A higher homologue of dimefluron served as an internal standard. The identity of the dimefluron metabolites in biological samples was confirmed using HPLC-MS experiments. The elimination study showed that the concentration maximum for dimefluron and its metabolites in rat faeces was reached 48 h after the administration of the parent drug. O-Desmethylated derivatives of dimefluron prevailed among the phase I metabolites.

• MeSH
• antitumorózní látky analýza   chemie   metabolismus   MeSH
• fluoreny analýza   chemie   metabolismus   MeSH
• hmotnostní spektrometrie metody   MeSH
• krysa rodu Rattus MeSH
• spektrofotometrie ultrafialová metody   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• dimefluron MeSH Prohlížeč
• fluoreny MeSH
• VUFB 13468 MeSH Prohlížeč

Benfluron (B) [5-(2-dimethylaminoethoxy)-7H-benzo[c]fluorene-7-one hydrochloride] is a potential antineoplastic agent. In the organism, B undergoes a rapid phase I biotransformation through oxidative and reductive metabolic pathways. The carbonyl reduction of B leads to reduced benfluron, red-B, this is one of the principal pathways for the deactivation of this compound. The structure of B was modified to suppress its rapid deactivation via the carbonyl reduction on C7. Dimefluron, D (3,9-dimethoxy-benfluron) is one of the derivatives of B, in which an alternative metabolic pathway (O-desmethylation) prevails over the carbonyl reduction. The goal of this study was to develop HPLC methods enabling chiral separations of the red-B and -D enantiomers. The separation of red-B enantiomers was successful done on a Chiralcel OD-R column (250 mm x 4.6 mm ID, 5 microm) using a mobile phase acetonitrile-1 M NaClO4 (40:60, v/v). Another mobile phase, methanol-1 M NaClO4 (75:25, v/v), had to be employed for the sufficient resolution of red-D enantiomers. Flow rate was 0.5 ml min(-1) in both cases. Red-B was detected at 340 nm, red-D at 370 nm. The above chiral HPLC methods were used for the study of the biotransformation of B and D in the microsomal fractions of liver homogenates prepared from various species (rat, rabbit, pig, guinea pig, goat and human). The enantiospecificity of the respective carbonyl reductases was evaluated and discussed for both prochiral compounds, B and D.

• MeSH
• alkoholoxidoreduktasy metabolismus   MeSH
• antitumorózní látky analýza   metabolismus   MeSH
• chromatografie kapalinová metody   MeSH
• druhová specificita MeSH
• fluoreny analýza   metabolismus   MeSH
• hospodářská zvířata MeSH
• játra chemie   metabolismus   MeSH
• králíci MeSH
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární konformace MeSH
• morčata MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv metody   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• morčata MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• alkoholoxidoreduktasy MeSH
• antitumorózní látky MeSH
• benzo(c)fluorene MeSH Prohlížeč
• fluoreny MeSH
• VUFB 13468 MeSH Prohlížeč

Benfluron (B, [5-(2-N-oxo-2-N',N"-dimethylaminoethoxy)-7-oxo-7H-benzo[c]fluorene]) is a potential benzo[c]fluorene antineoplastic agent with high activity against a broad spectrum of experimental tumors in vitro and in vivo. The structure of B has been modified to repress its rapid deactivation through carbonyl reduction on C7. 3,9-Dimethoxybenfluron (D, [3,9-dimethoxy-5-(2-N-oxo-2-N',N"-dimethylaminoethoxy)-7-oxo-7H-benzo[c]fluorene]) is one of the B derivatives developed. The present paper was designed to compare the C7 carbonyl reduction of B and D in microsomes, cytosol and hepatocytes from human liver. Two purified human enzymes, microsomal 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD 1) and cytosolic carbonyl reductase, were tested if they are responsible for B and D carbonyl reduction in the respective fractions. Indeed, carbonyl reduction of D in comparison to that of B was 4 and 6-10 times less extensive in human liver microsomes and cytosol, respectively. Moreover, about 10-20 times higher amounts of dihydro B than dihydro D were detected in primary culture of human hepatocytes. 11beta-HSD 1 was shown to be able to reduce B and D. For this enzyme, about 10 times higher rates of carbonyl reduction were observed for B than for D. Likewise, CR participates in B and D carbonyl reduction, although smaller amounts of both reduced metabolites were detected. In summary, carbonyl reduction of D was significantly less extensive than that of B in all in vitro experiments. This lower rate of D inactivation was especially pronounced in hepatocytes which represent a close to in vivo situation. Our results clearly demonstrate that dimethoxy substitution protects the carbonyl group of the benzo[c]fluorene moiety against the deactivation by microsomal and cytosolic reductases. Detailed knowledge on the participating enzymes may serve as a basis for the co-application of specific inhibitors in chemotherapy to further improve the pharmacokinetics of benzo[c]fluorene derivatives.

• MeSH
• 11-beta-hydroxysteroid dehydrogenasy MeSH
• alkoholoxidoreduktasy metabolismus   MeSH
• antitumorózní látky chemie   metabolismus   MeSH
• fluoreny chemie   metabolismus   MeSH
• hepatocyty enzymologie   metabolismus   MeSH
• hydroxysteroidní dehydrogenasy metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• oxidace-redukce MeSH
• subcelulární frakce MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 11-beta-hydroxysteroid dehydrogenasy MeSH
• 3,9-dimethoxybenfluron MeSH Prohlížeč
• alkoholoxidoreduktasy MeSH
• antitumorózní látky MeSH
• fluoreny MeSH
• hydroxysteroidní dehydrogenasy MeSH
• VUFB 13468 MeSH Prohlížeč

A non-enzymic system containing CuSO4 (10 mmol/L) and hydrogen peroxide (100 mmol/L) was used for the degradation of three polycyclic aromatic hydrocarbons: phenanthrene, fluoranthene, and pyrene (all at 10 mmol/L). The system degraded the compounds rapidly and efficiently. After 1 d at room temperature, more than 80% of pyrene, phenanthrene, and fluoranthene disappeared. Several products are formed during the reaction including a black precipitate.

• MeSH
• biodegradace MeSH
• fenantreny chemie   metabolismus   MeSH
• fluoreny chemie   metabolismus   MeSH
• látky znečišťující životní prostředí metabolismus   MeSH
• měď chemie   MeSH
• oxidace-redukce MeSH
• peroxid vodíku chemie   MeSH
• polycyklické aromatické uhlovodíky chemie   metabolismus   MeSH
• pyreny chemie   metabolismus   MeSH
• volné radikály chemie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenantreny MeSH
• fluoranthene MeSH Prohlížeč
• fluoreny MeSH
• látky znečišťující životní prostředí MeSH
• měď MeSH
• peroxid vodíku MeSH
• phenanthrene MeSH Prohlížeč
• polycyklické aromatické uhlovodíky MeSH
• pyrene MeSH Prohlížeč
• pyreny MeSH
• volné radikály MeSH