The release of hexavalent chromium [Cr (VI)] into environments has resulted in many undesirable interactions with biological systems for its toxic potential and mutagenicity. Chromate reduction via chromium reductase (ChrR) is a key strategy for detoxifying Cr (VI) to trivalent species of no toxicity. In this study, ten bacterial isolates were isolated from heavily polluted soils, with a strain assigned as FACU, being the most efficient one able to reduce Cr (VI). FACU was identified as Escherichia coli based on morphological and 16S rRNA sequence analyses. Growth parameters and enzymatic actions of FACU were tested under different experimental conditions, in the presence of toxic chromium species. The E. coli FACU was able to reduce chromate at 100 μg/mL conceivably by reducing Cr (VI) into the less harmful Cr (III). Two distinctive optical spectroscopic techniques have been employed throughout the study. Laser-induced breakdown spectroscopy (LIBS) was utilized as qualitative analysis to demonstrate the presence of chromium with the distinctive spectral lines for bacteria such as Ca, Fe, and Na. While UV-visible spectroscopy was incorporated to confirm the reduction capabilities of E. coli after comparing Cr (III) spectrum to that of bacterial product spectrum and they were found to be identical. The chromate reductase specific activity was 361.33 μmol/L of Cr (VI) per min per mg protein. The FACU (EMCC 2289) 16S rRNA sequence and the ChrR-partially isolated gene were submitted to the DDBJ under acc. # numbers LC177419 and LC179020, respectively. The results support that FACU is a promising source of ChrR capable of bioremediation of toxic chromium species.
- MeSH
- bakteriální léková rezistence MeSH
- biodegradace MeSH
- chrom metabolismus farmakologie MeSH
- Escherichia coli klasifikace izolace a purifikace metabolismus fyziologie MeSH
- fylogeneze MeSH
- karcinogeny životního prostředí metabolismus farmakologie MeSH
- oxidace-redukce MeSH
- oxidoreduktasy genetika metabolismus MeSH
- proteiny z Escherichia coli genetika metabolismus MeSH
- půdní mikrobiologie MeSH
- RNA ribozomální 16S genetika MeSH
- Publikační typ
- časopisecké články MeSH
The tumour suppressor p53 is one of the most important cancer genes. Previous findings have shown that p53 expression can influence DNA adduct formation of the environmental carcinogen benzo[a]pyrene (BaP) in human cells, indicating a role for p53 in the cytochrome P450 (CYP) 1A1-mediated biotransformation of BaP in vitro. We investigated the potential role of p53 in xenobiotic metabolism in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with BaP. BaP-DNA adduct levels, as measured by (32)P-postlabelling analysis, were significantly higher in liver and kidney of Trp53(-/-) mice than of Trp53(+/+) mice. Complementarily, significantly higher amounts of BaP metabolites were also formed ex vivo in hepatic microsomes from BaP-pretreated Trp53(-/-) mice. Bypass of the need for metabolic activation by treating mice with BaP-7,8-dihydrodiol-9,10-epoxide resulted in similar adduct levels in liver and kidney in all mouse lines, confirming that the influence of p53 is on the biotransformation of the parent compound. Higher BaP-DNA adduct levels in the livers of Trp53(-/-) mice correlated with higher CYP1A protein levels and increased CYP1A enzyme activity in these animals. Our study demonstrates a role for p53 in the metabolism of BaP in vivo, confirming previous in vitro results on a novel role for p53 in CYP1A1-mediated BaP metabolism. However, our results also suggest that the mechanisms involved in the altered expression and activity of the CYP1A1 enzyme by p53 in vitro and in vivo are different.
- MeSH
- adukty DNA metabolismus MeSH
- benzopyren metabolismus farmakokinetika MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- jaterní mikrozomy účinky léků metabolismus MeSH
- karcinogeny životního prostředí metabolismus farmakokinetika MeSH
- ledviny účinky léků metabolismus MeSH
- metabolická aktivace MeSH
- metabolická inaktivace MeSH
- mutantní kmeny myší MeSH
- myši inbrední C57BL MeSH
- NAD(P)H dehydrogenasa (chinon) metabolismus MeSH
- nádorový supresorový protein p53 genetika metabolismus MeSH
- poškození DNA účinky léků genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aflatoxins are potent hepatocarcinogen in animal models and suspected carcinogen in humans. The most important aflatoxin in terms of toxic potency and occurrence is aflatoxin B1 (AFB1). In this review, we mainly summarized the key metabolizing enzymes of AFB1 in animals and humans. Moreover, the interindividual and the interspecies differences in AFB1 metabolism are highly concerned. In human liver, CYP3A4 plays an important role in biotransforming AFB1 to the toxic product AFB1-8,9-epoxide. In human lung, CYP2A13 has a significant activity in metabolizing AFB1 to AFB1-8,9-epoxide and AFM1-8,9-epoxide. The epoxide of AFB1-8,9-epoxide could conjugate with glutathione to reduce the toxicity by glutathione-S-transferase (GST). In poultry species, CYP2A6, CYP3A37, CYP1A5, and CYP1A1 are responsible for bioactivation of AFB1. There are interindividual variations in the rate of activation of aflatoxins in various species, and there are also differences between children and adults. The age and living regions are important factors affecting resistance of species to AFB1. The rate of AFB1-8,9-epoxide formation and its conjugation with glutathione are key parameters in interspecies and interindividual differences in sensitivity to the toxic effect of AFB1. This review provides an important information for key metabolizing enzymes and the global metabolism of aflatoxins in different species.
- MeSH
- aflatoxin B1 metabolismus toxicita MeSH
- druhová specificita MeSH
- endoplazmatické retikulum účinky léků enzymologie MeSH
- játra účinky léků enzymologie metabolismus MeSH
- karcinogeny životního prostředí metabolismus toxicita MeSH
- lidé MeSH
- metabolická inaktivace MeSH
- plíce účinky léků enzymologie metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- respirační sliznice účinky léků enzymologie metabolismus MeSH
- střevní sliznice účinky léků enzymologie metabolismus MeSH
- systém (enzymů) cytochromů P-450 genetika metabolismus MeSH
- toxikokinetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Cílem práce byla analýza genotoxického rizika v MSK a posouzení významu genotoxických faktorů v etiologii nádorových onemocnění prostřednictvím propojení registru profesionálních expozic genotoxickým faktorům s nádorovým registrem a srovnání frekvence zjištěných nádorových onemocnění u osob profesionálně exponovaných genotoxickým faktorům v MSK s výskytem nádorových onemocnění u populace v České republice. Soubor tvořilo 748 osob, u nichž byly k dispozici záznamy o profesionální expozici od roku 2005, které byly alespoň 1x aktualizovány. Nejčastějšími karcinogeny byly polycyklické aromatické uhlovodíky (PAU), konkrétně benzo[a]pyren, benzo[d,e,f]chryzen a cytostatika aplikovaná ve zdravotnických zařízeních. Soubor byl propojen s nádorovým registrem v Ostravě v červnu 2009 a podruhé v červnu 2011. Bylo zjištěno 22 nádorových onemocnění v roce 2009 a 27 nádorových onemocnění v roce 2011. Nebyl zjištěn staticky významný rozdíl ve výskytu nádorových onemocnění (C 00–C 97, D 00–D 09) v daném souboru v letech 1996–2009 a výskytu nádorových onemocnění v populaci České republiky v daných věkových skupinách. V rámci provedených cytogenetických analýz lidských periferních lymfocytů byl zjištěn statisticky významný rozdíl (p = 0,043) v zastoupení případů nádorových onemocnění ve skupinách dle % AB.B. Největší výskyt byl ve skupině s větším výskytem (≥4 %) AB.B. Důvody pro relativně nízký výskyt nádorových onemocnění u osob exponovaných genotoxickým látkám mohou být ve snížení expozic genotoxickým látkám v důsledku opatření nařízených hygienickou službou po prokázání zvýšené hodnoty chromozomových aberací v rizikových provozech.
The object of this study is to present an analysis of genotoxic risks in the Moravian–Silesian Region and assess the significance of genotoxic factors in the etiology of cancer by bringing together the Registry of Occupational Exposure to Genotoxic Factors and Cancer Registry and compare the rate of detected cancer in persons professionally exposed to genotoxic factors in the Moravian–Silesian Region with the occurrence of cancer in the population of the Czech Republic. The set of individuals consisted of 748 subjects whose records of occupational exposure have been available since 2005 and have been updated at least once. The most common carcinogens were polycyclic aromatic hydrocarbons (PAHs), particularly benzo[a]pyrene, benzo[d,e,f]chrysene and cytostatics applied in healthcare facilities. The file was linked to the Cancer Registry in Ostrava in June 2009 and again in June 2011 with 22 cases of cancer recorded in 2009 and 27 cases of cancer in 2011. There was no statistically significant difference between the incidence of cancer (C 00–C 97, D 00–D 09) in the 1996–2009 cohort and the incidence of cancer in the population of the Czech Republic in the relevant age groups. A statistically significant difference (p = 0.043) was detected in cases of cancer in groups according to % AB.B. The greatest incidence was detected in the group with a higher incidence of (≥4%) AB.B. The reasons for the relatively low incidence of cancer in people exposed to genotoxic agents may be due to reduced exposure to genotoxic agents as a result of measures ordered by the Public Health Authority following demonstrably increased levels of chromosomal aberrations in high-risk environments.
- MeSH
- cytogenetické vyšetření metody MeSH
- karcinogeny životního prostředí * metabolismus škodlivé účinky MeSH
- látky znečišťující vzduch v pracovním prostředí * izolace a purifikace škodlivé účinky MeSH
- lidé MeSH
- nádory * epidemiologie etiologie genetika chemicky indukované klasifikace MeSH
- pracovní expozice * normy prevence a kontrola škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
o-Aminophenol and N-(2-methoxyphenyl)hydroxylamine are human metabolites of the industrial and environmental pollutant and bladder carcinogen 2-methoxyaniline (o-anisidine). The latter one is also a human metabolite of another pollutant and bladder carcinogen, 2-methoxynitrobenzene (o-nitroanisole). Here, we investigated the ability of rat hepatic micro- somes to metabolize these metabolites. N-(2-methoxyphenyl)hydroxylamine is metabolized by rat hepatic microsomes to o-aminophenol and predominantly o-anisidine, the parent carcinogen from which N-(2-methoxyphenyl)hydroxylamine is formed. In addition, two N-(2-methoxyphenyl)hydroxylamine metabolites, whose exact structures have not been identified as yet, were generated. On the contrary, no metabolites were found to be formed from o-aminophenol by rat hepatic microsomes. Whereas N-(2-methoxyphenyl)hydroxylamine is responsible for formation of three deoxyguanosine adducts in DNA, o-aminophenol seems to be a detoxication metabolite of N-(2-methoxyphenyl)hydroxylamine and/or a parental carcinogen, o-anisidine; no o-aminophenol-derived DNA adducts were found after its reaction with microsomal cytochromes P450 and peroxidases.
- MeSH
- aminofenoly metabolismus toxicita MeSH
- aniliny metabolismus toxicita MeSH
- biotransformace MeSH
- hydroxylaminy metabolismus toxicita MeSH
- játra metabolismus MeSH
- karcinogeny životního prostředí metabolismus toxicita MeSH
- krysa rodu rattus MeSH
- metabolická clearance MeSH
- metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
3-aminobenzanthrone (3-ABA) is the metabolite of the carcinogenic air pollutant 3-nitrobenzanthrone (3-NBA). 3-ABA was investigated for its ability to induce cytochrome P450 1A1 (CYP1A1) and NAD(P)H:quinone oxidoreductase (NQO1) in kidney and lung of rats, and for the influence of such induction on DNA adduct formation by 3-ABA and 3-NBA. NQO1 is the enzyme that reduces 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize 3-ABA to the same intermediate. When activated by cytosolic and and/or microsomal fractions isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney, both compounds generated the same DNA-adduct pattern, consisting of five adducts. When pulmonary cytosols isolated from rats that had been treated i.p. with 40 mg/kg bw of 3-ABA were incubated with 3-NBA, DNA adduct formation was up to 1.7-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. In contrast, no induction of NQO1 expression by 3-ABA treatment was found in the kidney. Incubations of 3-ABA with renal and pulmonary microsomes of 3-ABA-treated rats led to an increase of up to a 4.5-fold in DNA-adduct formation relative to controls. The stimulation of DNA-adduct formation correlated with a higher protein expression and activity of CYP1A1 induced by 3-ABA. These results show that by inducing lung and kidney CYP1A1 and NQO1, 3-ABA increases its own enzymatic activation as well as that of the environmental pollutant, 3-NBA, thereby enhancing the genotoxic and carcinogenic potential of both compounds.
- MeSH
- adukty DNA MeSH
- benz(a)anthraceny farmakologie metabolismus MeSH
- biotransformace MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- karcinogeny životního prostředí metabolismus MeSH
- krysa rodu rattus MeSH
- ledviny metabolismus účinky léků MeSH
- lidé MeSH
- mikrozomy enzymologie metabolismus účinky léků MeSH
- NAD(P)H dehydrogenasa (chinon) metabolismus MeSH
- plíce metabolismus účinky léků MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
We investigated the ability of hepatic microsomes from rat and rabbit to metabolize 2-methoxyaniline (o-anisidine), an industrial and environmental pollutant and a bladder carcinogen for rodents. Using HPLC combined with electrospray tandem mass spectrometry, we determined that o-anisidine is oxidized by microsomes of both species to N-(2-methoxyphenyl)hydroxylamine, o-aminophenol, and one additional metabolite, the exact structure of which has not been identified as yet. N-(2-Methoxyphenyl)hydroxylamine is either further oxidized to 2-methoxynitrosobenzene (o-nitrosoanisole) or reduced to parental o-anisidine, which can be oxidized again to produce o-aminophenol. To define the role of microsomal cytochromes P450 (P450) in o-anisidine metabolism, we investigated the modulation of this metabolism by specific inducers and selective inhibitors of these enzymes. The results of the studies suggest that o-anisidine is a promiscuous substrate of P450s of rat and rabbit liver; because P450s of 1A, 2B, 2E, and 3A subfamilies metabolize o-anisidine in hepatic microsomes of both studied species. Using purified enzymes of rat and rabbit (P450s 1A1, 1A2, 2B2, 2B4, 2E1, 2C3, 3A1, and 3A6), reconstituted with NADPH:P450 reductase, the ability of P450s 1A1, 1A2, 2B2, 2B4, 2E1, and 3A6 to metabolize o-anisidine was confirmed. In the reconstituted P450 system, rabbit P450 2E1 was the most efficient enzyme metabolizing o-anisidine. The data demonstrate the participation of different rat and rabbit P450s in o-anisidine metabolism and indicate that both experimental animal species might serve as suitable models to mimic the fate of o-anisidine in human.
- MeSH
- aniliny metabolismus MeSH
- financování organizované MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- inhibitory cytochromu P450 MeSH
- jaterní mikrozomy enzymologie metabolismus MeSH
- karcinogeny životního prostředí metabolismus MeSH
- králíci MeSH
- krysa rodu rattus MeSH
- metabolická inaktivace MeSH
- oxidace-redukce MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- anisoly farmakologie imunologie metabolismus MeSH
- biotransformace genetika účinky léků MeSH
- experimenty na zvířatech MeSH
- exprese genu MeSH
- finanční podpora výzkumu jako téma MeSH
- karcinogeny životního prostředí farmakologie metabolismus toxicita MeSH
- systém (enzymů) cytochromů P-450 MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il. ; 32 cm
Je sledován vliv genotypu a fenotypu cytochromů P450 2D6 a 2E1 na metabolismus,účinky a genotoxicitu styrenu a některých léků u lidí exponovaných v průmyslu,u dobrovolníků a experimentálních zvířat.Cílem je možnost prevence zdravotního rizika.
- MeSH
- cytochrom P-450 CYP2E1 MeSH
- genotyp MeSH
- karcinogeny životního prostředí metabolismus MeSH
- látky znečišťující životní prostředí MeSH
- pracovní expozice MeSH
- vystavení vlivu životního prostředí MeSH
- xenobiotika metabolismus MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- environmentální vědy
- pracovní lékařství
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
