Cytochrome P450 1B1 (CYP1B1) is an enzyme that has a unique tumor-specific pattern of expression and is capable of bioactivating a wide range of carcinogenic compounds. We have reported previously that coordinated upregulation of CYP1B1 by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and the aryl hydrocarbon receptor ligands, may increase bioactivation of promutagens, such as benzo[a]pyrene (BaP) in epithelial cells. Here, we extend those studies by describing a novel mechanism participating in the regulation of CYP1B1 expression, which involves activation of the p38 mitogen-activated protein kinase (p38) and mitogen- and stress-activated protein kinase 1 (MSK1). Using inhibitors of p38 and MSKs, as well as mouse embryonic cells derived from p38α-deficient and MSK1/2 double knockout mice, we show here that TNF-α potentiates CYP1B1 upregulation via the p38/MSK1 kinase cascade. Effects of this inflammatory cytokine on CYP1B1 expression further involve the positive transcription elongation factor b (P-TEFb). The inhibition of the P-TEFb subunit, cyclin-dependent kinase 9 (CDK9), which phosphorylates RNA polymerase II (RNAPII), prevented the enhanced CYP1B1 induction by a combination of BaP and inflammatory cytokine. Furthermore, using chromatin immunoprecipitation assays, we found that cotreatment of epithelial cells with TNF-α and BaP resulted in enhanced recruitment of both CDK9 and RNAPII to the Cyp1b1 gene promoter. Overall, these results have implications concerning the contribution of inflammatory factors to carcinogenesis, since enhanced CYP1B1 induction during inflammation may alter metabolism of exogenous carcinogens, as well as endogenous CYP1B1 substrates playing role in tumor development.

• MeSH
• cyklin-dependentní kinasa 9 genetika   MeSH
• cytochrom P450 CYP1B1 biosyntéza   genetika   MeSH
• cytokiny metabolismus   MeSH
• karcinogeneze účinky léků   genetika   MeSH
• karcinogeny toxicita   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 antagonisté a inhibitory   genetika   metabolismus   MeSH
• myši MeSH
• nádory chemicky indukované   genetika   patologie   MeSH
• pozitivní transkripční elongační faktor b genetika   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• RNA-polymerasa II genetika   MeSH
• signální transdukce účinky léků   MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We investigated the toxicity of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 μM), 1-NP (1 and 10 μM) and 3-NBA (0.5 and 5 μM). Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bulky DNA adducts even after 4-h treatment, suggesting rapid metabolic activation. Oxidative DNA damage was not affected. 1-NP caused protein oxidation and weak induction of lipid peroxidation after 4-h incubation. 3-NBA induced lipid peroxidation after 24-h treatment. Unlike B[a]P, induction of the aryl hydrocarbon receptor, measured as mRNA expression levels of CYP1A1 and CYP1B1, was low after treatment with polycyclic aromatic hydrocarbon (PAH) nitro-derivatives. All test compounds induced mRNA expression of NQO1, POR, and AKR1C2 after 24-h treatment. AKR1C2 expression indicates involvement of processes associated with reactive oxygen species generation. This was supported further by COX2 expression induced by 24-h treatment with 1-NP. In summary, 3-NBA was the most potent genotoxicant, whereas 1-NP exhibited the strongest oxidative properties.

• MeSH
• adukty DNA účinky léků   genetika   MeSH
• benz(a)anthraceny toxicita   MeSH
• benzopyren toxicita   MeSH
• buňky A549 MeSH
• cyklooxygenasa 2 genetika   MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• cytochrom P450 CYP1B1 genetika   MeSH
• hydroxysteroiddehydrogenasy genetika   MeSH
• lidé MeSH
• NAD(P)H dehydrogenasa (chinon) genetika   MeSH
• pneumocyty účinky léků   metabolismus   MeSH
• poškození DNA účinky léků   genetika   MeSH
• pyreny toxicita   MeSH
• systém (enzymů) cytochromů P-450 genetika   MeSH
• výfukové emise vozidel toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

UNLABELLED: Aristolochic acid I (AAI) is a plant drug found in Aristolochia species that causes aristolochic acid nephropathy, Balkan endemic nephropathy and their associated urothelial malignancies. AAI is activated via nitroreduction producing genotoxic N-hydroxyaristolactam, which forms DNA adducts. The major enzymes responsible for the reductive bioactivation of AAI are NAD(P)H: quinone oxidoreductase and cytochromes P450 (CYP) 1A1 and 1A2. Using site-directed mutagenesis we investigated the possible mechanisms of CYP1A1/1A2/1B1-catalyzed AAI nitroreduction. Molecular modelling predicted that the hydroxyl groups of serine122/threonine124 (Ser122/Thr124) amino acids in the CYP1A1/1A2-AAI binary complexes located near to the nitro group of AAI, are mechanistically important as they provide the proton required for the stepwise reduction reaction. In contrast, the closely related CYP1B1 with no hydroxyl group containing residues in its active site is ineffective in catalyzing AAI nitroreduction. In order to construct an experimental model, mutant forms of CYP1A1 and 1A2 were prepared, where Ser122 and Thr124 were replaced by Ala (CYP1A1-S122A) and Val (CYP1A2-T124V), respectively. Similarly, a CYP1B1 mutant was prepared in which Ala133 was replaced by Ser (CYP1B1-A133S). Site-directed mutagenesis was performed using a quickchange approach. Wild and mutated forms of these enzymes were heterologously expressed in Escherichia coli and isolated enzymes characterized using UV-vis spectroscopy to verify correct protein folding. Their catalytic activity was confirmed with CYP1A1, 1A2 and 1B1 marker substrates. Using (32)P-postlabelling we determined the efficiency of wild-type and mutant forms of CYP1A1, 1A2, and 1B1 reconstituted with NADPH:CYP oxidoreductase to bioactivate AAI to reactive intermediates forming covalent DNA adducts. The S122A and T124V mutations in CYP1A1 and 1A2, respectively, abolished the efficiency of CYP1A1 and 1A2 enzymes to generate AAI-DNA adducts. In contrast, the formation of AAI-DNA adducts was catalyzed by CYP1B1 with the A133S mutation. Our experimental model confirms the importance of the hydroxyl group possessing amino acids in the active center of CYP1A1 and 1A2 for AAI nitroreduction.

• MeSH
• adukty DNA metabolismus   MeSH
• aromatické hydroxylasy genetika   metabolismus   MeSH
• cytochrom P-450 CYP1A1 MeSH
• cytochrom P-450 CYP1A2 MeSH
• cytochrom P450 CYP1B1 MeSH
• katalytická doména genetika   MeSH
• katalýza MeSH
• kyseliny aristolochové metabolismus   MeSH
• lidé MeSH
• mutace * MeSH
• mutageneze cílená MeSH
• oxidace-redukce MeSH
• rekombinantní proteiny MeSH
• substrátová specifita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aryl hydrocarbon receptor (AhR) is highly expressed in psoriasis skin lesions. The aim of this study was to investigate serum concentrations of AhR, cytochromes P450 (CYP) 1A1 and 1B1 in patients with exacerbated psoriasis vulgaris treated with combined therapy of ultraviolet radiation (UVR) and crude coal tar. The analyses were performed by using enzyme-linked immunosorbent assays. Before the treatment, the patients had significantly higher serum levels of AhR and CYP1A1 than healthy controls. AhR median noticeably decreased after the therapy; nevertheless, it remained significantly higher compared to the controls. CYP1A1 levels measured before and after the therapy did not differ significantly. Serum CYP1A1 positively correlated with AhR values before and after the treatment. The serum values of CYP1B1 were very low and we did not see any differences between the study group and the control group. The study demonstrated that serum levels of AhR and CYP1A1 could indicate their immunopathological and metabolic roles in exacerbated psoriasis.

• MeSH
• cytochrom P-450 CYP1A1 krev   MeSH
• cytochrom P450 CYP1B1 krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• progrese nemoci * MeSH
• psoriáza krev   patologie   MeSH
• receptory aromatických uhlovodíků krev   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Antenatal glucocorticoid administration is used in cases of fetuses at risk to be born prematurely to enhance fetal pulmonary surfactant production and prevent infant respiratory distress syndrome. The CYP1A1 is the most important xenobiotic-metabolizing cytochrome P450 enzyme in the human placenta. Importantly, CYP1A1 generates reactive species and its placental activity is elevated in smoking women. CYP1A1 expression is mainly controlled by aryl hydrocarbon receptor (AHR) ligands. Glucocorticoid co-regulation of CYP1A1 has been described in various cell types but has not been systematically examined in the human placental trophoblast. We studied the effects of the glucocorticoids dexamethasone and betamethasone on inducibility of CYP1A1 and other AHR target genes CYP1A2, CYP1B1, UGT1A1 (UDP-glucuronosyltransferase 1A1) and BCRP (Breast cancer resistance protein) by prototype AHR ligand 3-methylcholanthrene (3MC) in isolated human placental trophoblast culture. We show that glucocorticoids alone had no effect on activity and protein/mRNA expression of CYP1A1 and little effect on mRNA expression of other AHR target genes. However, glucocorticoids significantly stimulated CYP1A1 mRNA, but not CYP1A2, CYP1B1, UGT1A1 and BCRP mRNAs, induction mediated by the AHR ligand. Consistently, glucocorticoids significantly augmented 7-ethoxyresorufin- O -deethylation (EROD) enzymatic activity in primary human placental trophoblast. Dexamethasone did not influence AHR and ARNT (Aryl hydrocarbon receptor nuclear translocator) mRNAs, suggesting that this phenomenon is not due to AHR or ARNT up-regulation by glucocorticoids in human trophoblast. In conclusion, our data suggest that glucocorticoids have no effect on AHR target genes expression per se , but they may potentiate CYP1A1 induction in human term placental trophoblast.

• MeSH
• aktivace transkripce genetika   účinky léků   MeSH
• betamethason farmakologie   MeSH
• cytochrom P-450 CYP1A1 * genetika   metabolismus   MeSH
• dexamethason farmakologie   MeSH
• exprese genu genetika   účinky léků   MeSH
• glukokortikoidy * farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• methylcholanthren farmakologie   MeSH
• placenta * cytologie   metabolismus   účinky léků   MeSH
• receptory aromatických uhlovodíků genetika   MeSH
• techniky in vitro MeSH
• transport proteinů genetika   účinky léků   MeSH
• trofoblasty cytologie   metabolismus   účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Associations of functional single nucleotide polymorphisms in cytochrome P450 1B1, epoxide hydrolase 1, NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase Pi-1 and deletions of glutathione S-transferases Mu-1 and θ-1 with colorectal cancer risk were investigated in a hospital-based case-control study on 495 matched pairs of Czech Caucasians. Polymorphisms were assessed by polymerase chain reaction restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction. Carriers of variant Ser allele in codon 453 of cytochrome P450 1B1 (rs1800440) were at a significantly lower risk of colorectal cancer compared to carriers of the wild-type allele (adjusted odds ratio, aOR=0.68, CI=0.51-0.89, p=0.006). The combination of polymorphisms in codons 453 and 432 (rs1056836) of cytochrome P450 1B1 further increased the protective effect (aOR=0.53, CI=0.34-0.83, p=0.005). The glutathione S-transferase Mu-1 deletion was associated with a moderately elevated colorectal cancer risk (aOR=1.30, CI=1.01-1.68, p=0.044). Combination of glutathione S-transferase Mu-1 and θ-1 deletion was associated with a significantly higher colorectal cancer risk compared to the presence of both full-length genes (aOR=1.58, CI=1.01-2.47, p=0.044). Genetic polymorphisms in glutathione S-transferase Pi-1, NAD(P)H:quinone oxidoreductase 1, epoxide hydrolase 1 and deduced epoxid hydrolase 1 activity did not modify the risk of colorectal cancer. These results provide further evidence that interaction between metabolic gene variants contributes to colorectal carcinogenesis.

• MeSH
• aromatické hydroxylasy MeSH
• dospělí MeSH
• epoxid hydrolasy genetika   MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• glutathion-S-transferasa fí genetika   MeSH
• glutathiontransferasa genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory enzymologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• NAD(P)H dehydrogenasa (chinon) genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• systém (enzymů) cytochromů P-450 genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Aryl hydrocarbon receptor (AHR) and its heterodimer aryl hydrocarbon nuclear translocator (ARNT) form a ligand-activated transcription complex that regulates expression of the AHR battery of target genes that includes the most important placental biotransformation enzyme cytochrome CYP1A1. Expression, placental localization, and ontogeny of AHR/Ahr and ARNT/Arnt have not been systematically studied in either human or rat placentas. Moreover, induction of such AHR target genes as CYP1A1, CYP1A2, CYP1B1, UGT1A1, and breast cancer resistance protein (BCRP), as well as of AHR, ARNT, and aryl hydrocarbon receptor repressor (AHRR) genes, after exposure to AHR ligands have not been studied in human placental trophoblast cultures. In this article, we show that only CYP1A1 messenger RNA (mRNA), but not CYP1A2, CYP1B1, UGT1A1, BCRP, AHR, ARNT, and AHRR mRNAs, is significantly induced in human term placental trophoblast cultures after exposure to prototype AHR ligands/activators 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, omeprazole, and β-naphthoflavone. We localized AHR/Ahr and ARNT/Arnt in rat placental trophoblasts throughout gestation and in first trimester and term human placental trophoblast, which comprise the crucial component of the maternal-fetal barrier. We demonstrate that rat Ahr and Cyp1a1 reached highest expression during gestation days 15 and 18, which might indicate different response to Ahr ligands in placental Cyp1a1 induction during rat gestation. We also propose the JEG3 choriocarcinoma cell line as a cellular model for human trophoblast induction studies through AHR. In conclusion, we describe expression and ontogeny of AHR/Ahr and ARNT/Arnt and systematically characterize induction of major AHR target genes in human placental trophoblast forming the placental maternal-fetal morphological and metabolic barrier.

• MeSH
• aktivace transkripce účinky léků   fyziologie   MeSH
• aromatické hydroxylasy genetika   metabolismus   MeSH
• choriokarcinom farmakoterapie   genetika   metabolismus   MeSH
• dospělí MeSH
• gestační stáří MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• nádorové buněčné linie MeSH
• potkani Wistar MeSH
• receptory aromatických uhlovodíků - jaderný translokátor genetika   metabolismus   MeSH
• receptory aromatických uhlovodíků genetika   metabolismus   MeSH
• těhotenství MeSH
• trofoblasty účinky léků   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• xenobiotika toxicita   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been positively associated with prostate cancer, but knowledge of the formation of PAH-DNA adducts and related genotoxic events in prostatic cells is limited. In the present study, benzo[a]pyrene (BaP), a potent mutagenic PAH, formed significant levels of DNA adducts in cell lines derived from human prostate carcinoma. When analyzing the effect of BaP on the induction of CYP1 enzymes participating in the metabolic activation of PAHs in LNCaP cells, we found that BaP induced expression of CYP1A1 and CYP1A2, but not CYP1B1 enzyme. Despite a significant amount of DNA adducts being formed by BaP and, to a lesser extent also by another strong genotoxin, dibenzo[a,l]pyrene, neither apoptosis nor cell-cycle arrest were induced in LNCaP cells. LNCaP cells were not sensitized to the induction of apoptosis by PAHs even through inhibition of the phosphoinositide-3-kinase/Akt pro-survival pathway. The lack of apoptosis was not due a disruption of expression of pro-apoptotic and pro-survival members of the Bcl-2 family of apoptosis regulators. In contrast to other genotoxic stimuli, genotoxic PAHs failed to induce DNA double-strand breaks, as illustrated by the lack of phosphorylation of histone H2AX or checkpoint kinase-2. BaP did not activate p53, as evidenced by the lack of p53 accumulation, phosphorylation at Ser15, or induction of p53 transcriptional targets. Taken together, although genotoxic PAHs produced significant levels of DNA adducts in a model of human prostate carcinoma cells, they did not activate the mechanisms leading to elimination of cells with significant damage to DNA, presumably due to their failure to activate the p53-dependent DNA damage response.

• MeSH
• apoptóza účinky léků   MeSH
• karcinom metabolismus   MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory prostaty metabolismus   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• poškození DNA účinky léků   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self-defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro-carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier-forming differentiated states in vitro. However, ethoxyresorufin O-deethylation (EROD) activity, the generation of reactive BaP metabolites and BaP-DNA adducts, were predominantly detected in differentiated NHU cell cultures. This gain-of-function was attributable to the expression of POR, an essential electron donor for all CYPs, which was significantly upregulated as part of urothelial differentiation. Immunohistology of muscle-invasive bladder cancer (MIBC) revealed significant overall suppression of POR expression. Stratification of MIBC biopsies into "luminal" and "basal" groups, based on GATA3 and cytokeratin 5/6 labeling, showed POR over-expression by a subgroup of the differentiated luminal tumors. In bladder cancer cell lines, CYP1-activity was undetectable/low in basal PORlo T24 and SCaBER cells and higher in the luminal POR over-expressing RT4 and RT112 cells than in differentiated NHU cells, indicating that CYP-function is related to differentiation status in bladder cancers. This study establishes POR as a predictive biomarker of metabolic potential. This has implications in bladder carcinogenesis for the hepatic versus local activation of carcinogens and as a functional predictor of the potential for MIBC to respond to prodrug therapies.

• MeSH
• buněčná diferenciace MeSH
• čipová analýza tkání MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• cytochrom P450 CYP1B1 genetika   MeSH
• down regulace MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory močového měchýře genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• urotel cytologie   metabolismus   MeSH
• xenobiotika farmakologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that interact in a complex manner with both the aryl hydrocarbon receptor (AhR) and estrogen receptors (ER). Their potential endocrine-disrupting activities may depend on both inhibitory AhR-ER cross-talk and on AhR-dependent metabolic production of estrogenic PAH metabolites. Here, we analyzed the impact of AhR on estrogen-like effects of PAHs, such as benzo[a]pyrene (BaP), in particular, on control of cell cycle progression/cell proliferation. Using AhR knockout variant of estrogen-sensitive human breast cancer MCF-7 cells (MCF-7 AhRKO cells), we observed that the AhR-dependent control of cytochrome P450 family 1 (CYP1) expression played a major role in formation of estrogenic BaP metabolites, most notably 3-OH-BaP, which contributed to the ER-dependent induction of cell cycle progression/cell proliferation. Both BaP metabolism and the BaP-induced S-phase transition/cell proliferation were inhibited in MCF-7 AhRKO cells, whereas these cells remained sensitive towards both endogenous estrogen 17β-estradiol or hydroxylated BaP metabolites. BaP was found to increase the activity of ER-dependent luciferase reporter gene in wild-type MCF-7 cells; however, unlike its hydroxylated metabolite, BaP failed to stimulate luciferase activity in MCF-7 AhRKO cells. Similarly, estrogen-like effects of other known estrogenic PAHs, such as benz[a]anthracene or 3-methylcholanthrene, were diminished in MCF-7 AhRKO cells. Ectopic expression of human CYP1A1 and CYP1B1 enzymes partly restored both BaP metabolism and its effects on cell proliferation. Taken together, our data suggest that the AhR-dependent metabolism of PAHs contributes significantly to the impact of PAHs on cell proliferation in estrogen-sensitive cells.

• MeSH
• buněčné kultury MeSH
• buněčný cyklus účinky léků   genetika   MeSH
• cytochrom P-450 CYP1A1 genetika   metabolismus   MeSH
• cytochrom P450 CYP1B1 genetika   metabolismus   MeSH
• endokrinní disruptory metabolismus   toxicita   MeSH
• exprese genu účinky léků   MeSH
• genetické vektory MeSH
• genový knockdown MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• plazmidy MeSH
• polycyklické aromatické uhlovodíky metabolismus   toxicita   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• receptory aromatických uhlovodíků genetika   metabolismus   MeSH
• receptory pro estrogeny genetika   metabolismus   MeSH
• reportérové geny MeSH
• transfekce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH