Chromosome analysis was conducted for peripheral lymphocytes of 23 printers exposed to toluene concentrations of 590 mg/m3 in a rotary machine workshop and to rotogravure printing inks. The percentages of aberrant cells were 2.30 in the printers and 1.46 in the control group (n = 22) (p < .05). The concentration of hippuric acid in printers was significantly higher than in the control group (p < .01), and the level of blood toluene at the end of the workshift was 0.500 mg/l. The authors also examined rotogravure printing inks-considered a potential source of genotoxic polycyclic aromatic hydrocarbons because they contained carbon black-their use in printing plants, and previous documentation of increased chromosomal aberrations in rotogravure printers. Only milligrams of fluorene and phenanthrene per gram of the printing inks were found; no polycyclic aromatic hydrocarbons with carcinogenic properties were discovered in the inks. The authors used Salmonella typhimurium indicator strains TA 98, TA 100, TA 1537, and YG 1041 in spot tests and indicator strains TA 98 and TA 100 in plate-incorporation assays to determine that there was no bacterial mutagenicity of all four colors of rotogravure inks. Urinary mutagenicity, which was evaluated with a microsuspension assay containing YG 1041 indicator strain both in the presence and absence of metabolic activation, was also studied. No significant difference in bacterial mutagenicity was found between the exposed and control groups. The increased percentage of aberrant cells in printers can be explained by exposure to genotoxicants that are not excreted in urine. Toluene was the most likely cause of the aberration.

• MeSH
• chromozomální aberace MeSH
• dospělí MeSH
• inkoust MeSH
• lidé středního věku MeSH
• lidé MeSH
• pracovní expozice analýza   MeSH
• testy genotoxicity metody   MeSH
• tiskařství MeSH
• toluen škodlivé účinky   moč   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• toluen MeSH

During the period of 1983-1985, in two of apprentice schools of P. town the health disorders were investigated in the total of 82 apprentices 15-18 years old from the environment with elevated concentrations of formaldehyde and toluene. The study was contrasted with a control total of 42 apprentices. Cytogenetical examination has been performed, and selected immunological parameters in both blood serum and saliva have been assessed with red and white blood cells counts including differential formula of white blood cells. In addition, the atmospheric toxicity of formaldehyde and vapours of organic solvents (toluene, xylene, varnish naphtha) was measured. A single biological exposure test has been performed for the detection toluene. Statistically significant were differences in occurrence of cell chromosomal aberrations between the group of long term formaldehyde and toluene exposure (averagely 3.53% ABB) and controls (2.21% ABB) as obtained in 1983 and 1984, and so were differences between the long term-to-toluene exposed group (3.30% ABB) and the above mentioned control group as obtained in 1984. No similar results were stated between the long term-to-formaldehyde exposed (3.07% ABB) and control (2.55% ABB) groups in 1985. The main evidence consisted in finding the genotoxical/clastogenic effect of observed agents associated with mainly chromosomal abnormalities of chromatide type. It outflowed from the determination of selected serum proteins (Ig and acute phase proteins) and salivary lysozyme that the group under the combined influence of formaldehyde and toluene showed significantly lower IgG and higher alpha-1-antitrypsin (A1AT). The group at risk of toluene was characteristical in elevated concentrations of alpha-2-macroglobulin (A2M) and A1AT. Most pronounced changes in first year had been revealed through the evaluation of the influence of the duration at risk (significant decrease in IgA and prealbumin, and the increase in A2M and A1AT). The infectious disease as experienced 2 month prior the collection resulted in a significant decrease of IgM, A2M and A1AT in risky groups in individuals with infection in anamnesis. Salivary lysozyme concentration of apprentice environmentally exposed to formaldehyde in the noon showed the decrease, whereas its increase occurred in controls with the difference on 5% significancy level. Blood count assessements showed no significant differences between the investigated values as well as any were assessed between the incidence of health disorders of apprentices and their correspondance to the given group.

• MeSH
• chromozomální aberace MeSH
• formaldehyd škodlivé účinky   analýza   MeSH
• krevní obraz MeSH
• krevní proteiny analýza   MeSH
• látky znečišťující vzduch v pracovním prostředí škodlivé účinky   analýza   MeSH
• lidé MeSH
• mladiství MeSH
• monitorování životního prostředí * MeSH
• rozpouštědla škodlivé účinky   analýza   MeSH
• toluen škodlivé účinky   analýza   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• formaldehyd MeSH
• krevní proteiny MeSH
• látky znečišťující vzduch v pracovním prostředí MeSH
• rozpouštědla MeSH
• toluen MeSH

From 3-(3,4-dimethoxyphenyl)propenic acid chloride and substituted amines and hydrazides, the appropriate amides and hydrazides (Table 1) were synthesized at 60-80 degrees C in the medium of benzene or toluene. The reaction of this chloride with benzaldehyde hydrazone at 70-80 degrees C yielded N,N'-bis[3-(3,4-dimethoxyphenyl)propenoyl]hydrazine (VIII). At ambient temperature the benzylidene hydrazide of 3-(3,4-dimethoxyphenyl)propenic acid (VII) and a small amount of compound VIII were isolated. In the reaction of 3-(3,4-dimethoxyphenyl)propenic acid chloride with benzylidene hydrazide (VII) at 70-80 degrees C, compound VIII was obtained (Scheme 1). Compounds I, VII, VIII and IX possessed higher indices of increase in fortnight tests of the first degree in the roosters of meat hybrides compared to the negative control, but the indices of conversion were unfavourable. The compounds did not reach the efficacy of the avoparcin standard. Derivatives II and VI possessed 67.5 and 63.5%, respectively, of anthelmintic activity of levamisol against Nippostrongylus brasiliensis. The prepared compounds were not antibacterially effective and they were not mutagenic in the tests following the method of Ames, either.

• MeSH
• Bacteria účinky léků   MeSH
• cinnamáty chemická syntéza   farmakologie   MeSH
• léčivé přípravky * MeSH
• Nippostrongylus účinky léků   MeSH
• testy genotoxicity MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• 3-(3,4-dimethoxyphenyl)propenoic acid MeSH Prohlížeč
• cinnamáty MeSH
• léčivé přípravky * MeSH

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues.

• MeSH
• antagonisté estrogenu farmakologie   MeSH
• benz(a)anthraceny toxicita   MeSH
• benzopyren toxicita   MeSH
• benzothiazoly MeSH
• bromodeoxyuridin metabolismus   MeSH
• buněčný cyklus účinky léků   MeSH
• epigeneze genetická MeSH
• estradiol analogy a deriváty   farmakologie   MeSH
• fulvestrant MeSH
• karcinogeny toxicita   MeSH
• karcinom farmakoterapie   genetika   metabolismus   MeSH
• lékové interakce MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 antagonisté a inhibitory   genetika   metabolismus   MeSH
• nádory prsu farmakoterapie   genetika   metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• receptory pro estrogeny MeSH
• replikace DNA účinky léků   MeSH
• thiazoly farmakologie   MeSH
• toluen analogy a deriváty   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté estrogenu MeSH
• benz(a)anthracene MeSH Prohlížeč
• benz(a)anthraceny MeSH
• benzopyren MeSH
• benzothiazoly MeSH
• bromodeoxyuridin MeSH
• estradiol MeSH
• fulvestrant MeSH
• karcinogeny MeSH
• nádorový supresorový protein p53 MeSH
• pifithrin MeSH Prohlížeč
• receptory pro estrogeny MeSH
• thiazoly MeSH
• toluen MeSH

Results of a recent molecular epidemiological study of 1,3-butadiene (BD) exposed Czech workers, conducted to compare female to male responses, have confirmed and extended the findings of a previously reported males only study (HEI Research Report 116, 2003). The initial study found that urine concentrations of the metabolites 1,2-dihydroxy-4-(acetyl) butane (M1) and 1-dihydroxy-2-(N-acetylcysteinyl)-3-butene (M2) and blood concentrations of the hemoglobin adducts N-[2-hydroxy-3-butenyl] valine (HB-Val) and N-[2,3,4-trihydroxy-butyl] valine (THB-Val) constitute excellent biomarkers of exposure, both being highly correlated with BD exposure levels, and that GST genotypes modulate at least one metabolic pathway, but that irreversible genotoxic effects such as chromosome aberrations and HPRT gene mutations are neither associated with BD exposure levels nor with worker genotypes (GST [glutathione-S-transferase]-M1, GSTT1, CYP2E1 (5' promoter), CYP2E1 (intron 6), EH [epoxide hydrolase] 113, EH139, ADH [alcohol dehydrogenase]2 and ADH3). The no observed adverse effect level (NOAEL) for chromosome aberrations and HPRT mutations was 1.794 mg/m(3) (0.812 ppm)--the mean exposure level for the highest exposed worker group in this initial study. The second Czech study, reported here, initiated in 2003, included 26 female control workers, 23 female BD exposed workers, 25 male control workers and 30 male BD exposed workers (some repeats from the first study). Multiple external exposure measurements (10 full 8-h shift measures by personal monitoring per worker) over a 4-month period before biological sample collections showed that BD workplace levels were lower than in the first study. Mean 8-h TWA exposure levels were 0.008 mg/m(3) (0.0035 ppm) and 0.397 mg/m(3) (0.180 ppm) for female controls and exposed, respectively, but with individual single 8-h TWA values up to 9.793 mg/m(3) (4.45 ppm) in the exposed group. Mean male 8-h TWA exposure levels were 0.007 mg/m(3) (0.0032 ppm) and 0.808 mg/m(3) (0.370 ppm) for controls and exposed, respectively; however, the individual single 8-h TWA values up to 12.583 mg/m(3) (5.72 ppm) in the exposed group. While the urine metabolite concentrations for both M1 and M2 were elevated in exposed compared to control females, the differences were not significant, possibly due to the relatively low BD exposure levels. For males, with greater BD exposures, the concentrations of both metabolites were significantly elevated in urine from exposed compared to control workers. As in the first study, urine metabolite excretion patterns in both sexes revealed conjugation to be the minor detoxification pathway (yielding the M2 metabolite) but both M1 and M2 concentration values were lower in males in this second study compared to their concentrations in the first, reflecting the lower external exposures of males in this second study compared to the first. Of note, females showed lower concentrations of both M1 and M2 metabolites in the urine per unit of BD exposure than did males while exhibiting the same M1/(M1+M2) ratio, reflecting the same relative utilization of the hydrolytic (producing M1) and the conjugation (producing M2) detoxification pathways as males. Assays for the N,N-(2,3-dihydroxy-1,4-butadyl) valine (pyr-Val) hemoglobin (Hb) adduct, which is specific for the highly genotoxic 1,2,3,4-diepoxybutane (DEB) metabolite of BD, have been conducted on blood samples from all participants in this second Czech study. Any adduct that may have been present was below the limits of quantitation (LOQ) for this assay for all samples, indicating that production of this important BD metabolite in humans is below levels produced in both mice and rats exposed to as little as 1.0 ppm BD by inhalation (J.A. Swenberg, M.G. Bird, R.J. Lewis, Future directions in butadiene risk assessment, Chem. Biol. Int. (2006), this issue). Results of assays for the HB-Val and THB-Val hemoglobin adducts are pending. HPRT mutations, determined by cloning assays, and multiple measures of chromosome level changes (sister-chromatid exchanges [SCE], aberrations determined by conventional methods and FISH) again showed no associations with BD exposures, confirming the findings of the initial study that these irreversible genotoxic changes do not arise in humans occupationally exposed to low levels of BD. Except for lower production of both urine metabolites in females, no female-male differences in response to BD exposures were detected in this study. As in the initial study, there were no significant genotype associations with the irreversible genotoxic endpoints. However, as in the first, differences in the metabolic detoxification of BD as reflected in relative amounts of the M1 and M2 urinary metabolites were associated with genotypes, this time both GST and EH.

• MeSH
• acetylcystein analogy a deriváty   moč   MeSH
• benzen analýza   MeSH
• butadieny aplikace a dávkování   škodlivé účinky   MeSH
• chemický průmysl * MeSH
• chromozomální aberace účinky léků   MeSH
• dospělí MeSH
• genotyp MeSH
• hemoglobiny metabolismus   MeSH
• hypoxanthinfosforibosyltransferasa genetika   MeSH
• lidé MeSH
• molekulární epidemiologie MeSH
• mutace genetika   MeSH
• pohlavní dimorfismus * MeSH
• pracovní expozice škodlivé účinky   statistika a číselné údaje   MeSH
• pracovní síly MeSH
• styren analýza   MeSH
• toluen analýza   MeSH
• výměna sesterských chromatid účinky léků   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• 1-hydroxy-2-(N-acetylcysteinyl)-3-butene MeSH Prohlížeč
• 1,2-dihydroxy-4-(N-acetylcysteinyl)butane MeSH Prohlížeč
• 1,3-butadiene MeSH Prohlížeč
• acetylcystein MeSH
• benzen MeSH
• butadieny MeSH
• hemoglobiny MeSH
• hypoxanthinfosforibosyltransferasa MeSH
• styren MeSH
• toluen MeSH

Environmental compartments polluted with animal charcoal from the skin and hide cottage industries are rich in toxic heavy metals and diverse hydrocarbon classes, some of which are carcinogenic, mutagenic, and genotoxic, and thus require a bio-based eco-benign decommission strategies. A shotgun metagenomic approach was used to decipher the microbiome, hydrocarbon degradation genes, and heavy metal resistome of a microbial consortium (FN8) from an animal-charcoal polluted site enriched with fluorene. Structurally, the FN8 microbial consortium consists of 26 phyla, 53 classes, 119 orders, 245 families, 620 genera, and 1021 species. The dominant phylum, class, order, family, genus, and species in the consortium are Proteobacteria (51.37%), Gammaproteobacteria (39.01%), Bacillales (18.09%), Microbulbiferaceae (11.65%), Microbulbifer (12.21%), and Microbulbifer sp. A4B17 (19.65%), respectively. The microbial consortium degraded 57.56% (28.78 mg/L) and 87.14% (43.57 mg/L) of the initial fluorene concentration in 14 and 21 days. Functional annotation of the protein sequences (ORFs) of the FN8 metagenome using the KEGG GhostKOALA, KofamKOALA, NCBI's conserved domain database, and BacMet revealed the detection of hydrocarbon degradation genes for benzoate, aminobenzoate, polycyclic aromatic hydrocarbons (PAHs), chlorocyclohexane/chlorobenzene, chloroalkane/chloroalkene, toluene, xylene, styrene, naphthalene, nitrotoluene, and several others. The annotation also revealed putative genes for the transport, uptake, efflux, and regulation of heavy metals such as arsenic, cadmium, chromium, mercury, nickel, copper, zinc, and several others. Findings from this study have established that members of the FN8 consortium are well-adapted and imbued with requisite gene sets and could be a potential bioresource for on-site depuration of animal charcoal polluted sites.

• Klíčová slova
• Animal charcoal pollution, Biodegradation, Fluorene, Heavy metal resistome, Hydrocarbon degradation genes, Shotgun metagenomics,
• MeSH
• biodegradace MeSH
• dřevěné a živočišné uhlí MeSH
• fluoreny MeSH
• Gammaproteobacteria * MeSH
• látky znečišťující půdu * analýza   MeSH
• lidé MeSH
• mikrobiota * genetika   MeSH
• polycyklické aromatické uhlovodíky * metabolismus   MeSH
• půda MeSH
• půdní mikrobiologie MeSH
• těžké kovy * MeSH
• uhlovodíky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dřevěné a živočišné uhlí MeSH
• fluorene MeSH Prohlížeč
• fluoreny MeSH
• látky znečišťující půdu * MeSH
• polycyklické aromatické uhlovodíky * MeSH
• půda MeSH
• těžké kovy * MeSH
• uhlovodíky MeSH

Cytotoxicity and apoptosis induced by etoposide were studied during 72 hr in human melanoma cells. Etoposide initiated DNA-damage signaling via ATM kinase and activated p53 pathway and caspase-2. In response to treatment with etoposide, mitochondria of melanoma cells first increased their abundance and activity, and at later treatment intervals their dynamic behavior and functions became suppressed. Observed mitochondrial perturbation was not preceded by membrane potential loss but cytochrome c release was observed together with a rise in caspase-9 and caspase-3 activities. The pharmacological inhibition of relevant induced targets proved the importance of ATM and caspase-2 in etoposide-mediated cytotoxicity and apoptosis.

• MeSH
• adenosintrifosfát metabolismus   MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• apoptóza účinky léků   MeSH
• ATM protein MeSH
• benzothiazoly farmakologie   MeSH
• cyklosporin farmakologie   MeSH
• cysteinové endopeptidasy metabolismus   MeSH
• DNA vazebné proteiny antagonisté a inhibitory   metabolismus   MeSH
• etoposid farmakologie   MeSH
• inhibitory cysteinových proteinas farmakologie   MeSH
• inhibitory kaspas MeSH
• inhibitory proteinkinas farmakologie   MeSH
• kaspasa 2 metabolismus   MeSH
• kaspasa 3 metabolismus   MeSH
• kaspasa 9 metabolismus   MeSH
• lidé MeSH
• melanom patologie   MeSH
• mitochondrie účinky léků   MeSH
• nádorové buňky kultivované účinky léků   MeSH
• nádorové proteiny antagonisté a inhibitory   metabolismus   MeSH
• nádorové supresorové proteiny antagonisté a inhibitory   metabolismus   MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• poškození DNA MeSH
• protein X asociovaný s bcl-2 metabolismus   MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   metabolismus   MeSH
• proteiny buněčného cyklu antagonisté a inhibitory   metabolismus   MeSH
• superoxidy metabolismus   MeSH
• toluen analogy a deriváty   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfát MeSH
• antitumorózní látky fytogenní MeSH
• ATM protein, human MeSH Prohlížeč
• ATM protein MeSH
• BAX protein, human MeSH Prohlížeč
• benzothiazoly MeSH
• CASP2 protein, human MeSH Prohlížeč
• cyklosporin MeSH
• cysteinové endopeptidasy MeSH
• DNA vazebné proteiny MeSH
• etoposid MeSH
• inhibitory cysteinových proteinas MeSH
• inhibitory kaspas MeSH
• inhibitory proteinkinas MeSH
• kaspasa 2 MeSH
• kaspasa 3 MeSH
• kaspasa 9 MeSH
• nádorové proteiny MeSH
• nádorové supresorové proteiny MeSH
• nádorový supresorový protein p53 MeSH
• pifithrin MeSH Prohlížeč
• protein X asociovaný s bcl-2 MeSH
• protein-serin-threoninkinasy MeSH
• proteiny buněčného cyklu MeSH
• superoxidy MeSH
• toluen MeSH