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https://www.readbyqxmd.com/read/28104439/up-regulation-of-cyp1a1-and-phase-ii-enzymes-by-5-ring-isomeric-polycyclic-aromatic-hydrocarbons-in-precision-cut-rat-hepatic-slices-importance-of-molecular-shape
#1
Daphnee Pushparajah, Dfv Lewis, Costas Ioannides
The objectives of the present study were two-fold: (a) to evaluate the role of molecular shape on the interaction of polycyclic aromatic hydrocarbons (PAHs) with the Ah receptor and CYP1A1 upregulation, and (b) to evaluate the potential of PAHs to induce epoxide hydrolase and glutathione S-transferase, two major enzymes in their metabolism. In order to achieve these objectives, precision-cut rat liver slices were incubated with a range of concentrations of seven 5-ring isomeric PAHs, namely benzo[c]chrysene, benzo[b]chrysene, benzo[g]chrysene, dibenzo[a,j]anthracene, dibenzo[a,c]anthracene, picene and pentacene, for 24h...
January 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28103884/aryl-hydrocarbon-receptor-cytochrome-p450%C3%A2-1a1-pathway-mediates-breast-cancer-stem-cells-expansion-through-pten-inhibition-and-%C3%AE-catenin-and-akt-activation
#2
Abdullah Al-Dhfyan, Ali Alhoshani, Hesham M Korashy
BACKGROUND: Breast cancer stem cells (CSCs) are small sub-type of the whole cancer cells that drive tumor initiation, progression and metastasis. Recent studies have demonstrated a role for the aryl hydrocarbon receptor (AhR)/cytochrome P4501A1 pathway in CSCs expansion. However, the exact molecular mechanisms remain unclear. METHODS: The current study was designed to a) determine the effect of AhR activation and inhibition on breast CSCs development, maintenance, self-renewal, and chemoresistance at the in vitro and in vivo levels and b) explore the role of β-Catenin, PI3K/Akt, and PTEN signaling pathways...
January 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28089731/investigation-of-polymorphisms-in-genes-involved-in-estrogen-metabolism-in-menstrual-migraine
#3
Heidi G Sutherland, Morgane Champion, Amelie Plays, Shani Stuart, Larisa M Haupt, Alison Frith, E Anne MacGregor, Lyn R Griffiths
Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and >50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism...
January 13, 2017: Gene
https://www.readbyqxmd.com/read/28074113/genetic-polymorphisms-of-human-cytochrome-p450-cyp1a1-in-an-egyptian-population-and-tobacco-induced-lung-cancer
#4
Nada Ezzeldin, Dalia El-Lebedy, Amira Darwish, Ahmed El-Bastawisy, Mirhane Hassan, Shereen Abd El-Aziz, Mohamed Abdel-Hamid, Amal Saad-Hussein
BACKGROUND: Cytochrome P450 CYP1A1 helps detoxify the potential carcinogens in tobacco smoke, it was reported that polymorphisms in the coding gene result in variation in the expression and activity levels which alter metabolism and clearance of carcinogens and therefore modify cancer risk. In this work, we aimed to identify CYP1A1 gene polymorphisms associated with lung cancer in Egyptian population and to examine the interaction effect with Tobacco smoking in modulating disease risk...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28063306/constitutive-expression-and-activity-of-cytochrome-p450-in-conventional-pigs
#5
Søren Drud Nielsen, Yvonne Bauhaus, Galia Zamaratskaia, Matheus Antunes Junqueira, Karoline Blaabjerg, Bjørn Petrat-Melin, Jette Feveile Young, Martin Krøyer Rasmussen
Pigs have often been suggested to be a useful model for humans, when investigating CYP dependent events, like drug metabolism. However, comprehensive knowledge about the constitutive expression of the major CYP and corresponding transcription factors is limited. We compared the constitutive mRNA expression of aryl hydrocarbon receptor, constitutive androstane receptor and pregnane X receptor and CYP1A1, CYP1A2, CYP2A, CYP2E1 and CYP3A in liver, adipose tissue, muscle and small intestine in pigs, as well as the expression along the length of the small intestine and colon...
December 23, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/28063149/modulation-of-benzo-a-pyrene-induced-anxiolytic-like-behavior-by-retinoic-acid-in-zebrafish-involvement-of-oxidative-stress-and-antioxidant-defense-system
#6
Ratnalipi Mohanty, Saroj Kumar Das, Manorama Patri
Benzo[a]pyrene (B[a]P) is commonly associated with oxidative stress-induced neurotoxicity. Retinoic acid (RA) has been shown to exhibit neuroprotection in brain, and disruption of RA signaling via excess or deficient RA can lead to oxidative stress. B[a]P contamination in aquatic environment has been shown to lower the internal RA level. Thus, the present study was conducted in wild-type zebrafish to ameliorate the neurotoxic effect of B[a]P by waterborne RA co-supplementation. Findings showed that B[a]P induced anxiolytic-like behavioral response, and altered antioxidant activity in zebrafish is attenuated by RA...
January 6, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28058446/hepatotoxic-effects-of-cyproconazole-and-prochloraz-in-wild-type-and-hcar-hpxr-mice
#7
Philip Marx-Stoelting, Katrin Ganzenberg, Constanze Knebel, Flavia Schmidt, Svenja Rieke, Helen Hammer, Felix Schmidt, Oliver Pötz, Michael Schwarz, Albert Braeuning
The agricultural fungicides cyproconazole and prochloraz exhibit hepatotoxicity in rodent studies and are tumorigenic following chronic exposure. Both substances are suspected to act via a CAR (constitutive androstane receptor)/PXR (pregnane-X-receptor)-dependent mechanism. Human relevance of these findings is under debate. A 28-day toxicity study was conducted in mice with humanized CAR and PXR (hCAR/hPXR) with two dose levels (50 or 500 ppm) of both substances, using the model CAR activator phenobarbital as a reference...
January 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28052772/placental-mitochondrial-dna-and-cyp1a1-gene-methylation-as-molecular-signatures-for-tobacco-smoke-exposure-in-pregnant-women-and-the-relevance-for-birth-weight
#8
Bram G Janssen, Wilfried Gyselaers, Hyang-Min Byun, Harry A Roels, Ann Cuypers, Andrea A Baccarelli, Tim S Nawrot
BACKGROUND: Maternal smoking during pregnancy results in an increased risk of low birth weight through perturbations in the utero-placental exchange. Epigenetics and mitochondrial function in fetal tissues might be molecular signatures responsive to in utero tobacco smoke exposure. METHODS: In the framework of the ENVIRONAGE birth cohort, we investigated the effect of self-reported tobacco smoke exposure during pregnancy on birth weight and the relation with placental tissue markers such as, (1) relative mitochondrial DNA (mtDNA) content as determined by real-time quantitative PCR, (2) DNA methylation of specific loci of mtDNA (D-loop and MT-RNR1), and (3) DNA methylation of the biotransformation gene CYP1A1 (the last two determined by bisulfite-pyrosequencing)...
January 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28052106/a-prediction-algorithm-for-drug-response-in-patients-with-mesial-temporal-lobe-epilepsy-based-on-clinical-and-genetic-information
#9
Mariana S Silva-Alves, Rodrigo Secolin, Benilton S Carvalho, Clarissa L Yasuda, Elizabeth Bilevicius, Marina K M Alvim, Renato O Santos, Claudia V Maurer-Morelli, Fernando Cendes, Iscia Lopes-Cendes
Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy...
2017: PloS One
https://www.readbyqxmd.com/read/28049037/role-of-cyp1a1-in-the-biological-activity-of-methylated-resveratrol-analogue-3-4-5-4-tetramethoxystilbene-dmu-212-in-ovarian-cancer-a-2780-and-non-cancerous-hose-cells
#10
Hanna Piotrowska-Kempisty, Agnieszka Klupczyńska, Dorota Trzybulska, Katarzyna Kulcenty, Anna Maria Sulej-Suchomska, Małgorzata Kucińska, Renata Mikstacka, Marcin Wierzchowski, Marek Murias, Wanda Baer-Dubowska, Zenon Kokot, Jadwiga Jodynis-Liebert
The role of CYP1A1 and CYP1B1 enzymes in the biotransformation and biological activity of the methylated resveratrol analogue, 3,4,5,4'-tetramethoxystilbene (DMU-212) is still elusive. Our recently published data have shown that one of the metabolites of DMU-212, 3'-hydroxy-3,4,5,4'-tetramethoxystilbene (DMU-214) exerts more potent cytotoxic effects in A-2780 ovarian cancer cell line, as compared to the parent compound. Hence, this study aims to elucidate whether the biological activity of DMU-212 is related to its biotransformation to DMU-214...
December 31, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/28031317/coffee-intake-cardiovascular-disease-and-all-cause-mortality-observational-and-mendelian-randomization-analyses-in-95%C3%A2-000-223%C3%A2-000-individuals
#11
Ask Tybjærg Nordestgaard, Børge Grønne Nordestgaard
BACKGROUND: Coffee has been associated with modestly lower risk of cardiovascular disease and all-cause mortality in meta-analyses; however, it is unclear whether these are causal associations. We tested first whether coffee intake is associated with cardiovascular disease and all-cause mortality observationally; second, whether genetic variations previously associated with caffeine intake are associated with coffee intake; and third, whether the genetic variations are associated with cardiovascular disease and all-cause mortality...
December 28, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28018104/cyp1a1-cyp2e1-and-ephx1-polymorphisms-in-sporadic-colorectal-neoplasms
#12
Glaucia Maria M Fernandes, Anelise Russo, Marcela Alcântara Proença, Nathalia Fernanda Gazola, Gabriela Helena Rodrigues, Patrícia Matos Biselli-Chicote, Ana Elizabete Silva, João Gomes Netinho, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo
AIM: To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer (SCRC) risk. METHODS: Six hundred forty-one individuals (227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1*2A, CYP1A1*2C CYP2E1*5B and CYP2E1*6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28007926/circadian-regulation-of-benzo-a-pyrene-metabolism-and-dna-adduct-formation-in-breast-cells-and-the-mouse-mammary-gland
#13
Emily E Schmitt, Rola Barhoumi, Richard P Metz, Weston W Porter
The circadian clock plays a role in many biological processes, yet very little is known about its role in metabolism of drugs and carcinogens. The purpose of this study was to define the impact of circadian rhythms on benzo-a-pyrene (BaP) metabolism in the mouse mammary gland and develop a circadian in vitro model for investigating changes in BaP metabolism resulting from cross-talk between the molecular clock and aryl hydrocarbon receptor. Female 129sv mice (12 weeks old) received a single gavage dose of 50 mg/kg BaP at either noon or midnight, and mammary tissues were isolated 4 or 24 hours later...
December 22, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/28005143/acidic-cellular-microenvironment-modifies-carcinogen-induced-dna-damage-and-repair
#14
Q Shi, L Maas, C Veith, F J Van Schooten, R W Godschalk
Chronic inflammation creates an acidic microenvironment, which plays an important role in cancer development. To investigate how low pH changes the cellular response to the carcinogen benzo[a]pyrene (B[a]P), we incubated human pulmonary epithelial cells (A549 and BEAS-2B) with nontoxic doses of B[a]P using culturing media of various pH's (extracellular pH (pHe) of 7.8, 7.0, 6.5, 6.0 and 5.5) for 6, 24 and 48 h. In most incubations (pHe 7.0-6.5), the pH in the medium returned to the physiological pH 7.8 after 48 h, but at the lowest pH (pHe < 6...
December 22, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27966929/combined-docking-and-quantum-chemical-study-on-cyp-mediated-metabolism-of-estrogens-in-man
#15
Anikó Lábas, Balázs Krámos, Julianna Oláh
Long-term exposure to estrogens seriously increases the incidence of various diseases including breast cancer. Experimental studies indicate that cytochrome P450 (CYP) enzymes catalyze the bioactivation of estrogens to catechols, which can exert their harmful effects via various routes. It has been shown that the 4-hydroxylation pathway of estrogens is the most malign, while 2-hydroxylation is considered a benign pathway. It is also known experimentally that with increasing unsaturation of ring B of estrogens the prevalence of the 4-hydroxylation pathway significantly increases...
December 14, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27959388/a-tryptophan-derivative-ite-enhances-liver-cell-metabolic-functions-in%C3%A2-vitro
#16
Xiaoqian Zhang, Juan Lu, Bin He, Lingling Tang, Xiaoli Liu, Danhua Zhu, Hongcui Cao, Yingjie Wang, Lanjuan Li
Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotra-nsformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27956118/genetic-polymorphisms-of-phase-i-metabolizing-enzyme-genes-their-interaction-with-lifetime-grilled-and-smoked-meat-intake-and-breast-cancer-incidence
#17
Humberto Parada, Susan E Steck, Rebecca J Cleveland, Susan L Teitelbaum, Alfred I Neugut, Regina M Santella, Marilie D Gammon
PURPOSE: To examine associations between 22 CYP single nucleotide polymorphisms (SNPs) and breast cancer incidence and their interactions with grilled-smoked meat intake, a source of polycyclic aromatic hydrocarbons. METHODS: White women with first primary in situ or invasive breast cancer (n = 988) and frequency-matched controls (n = 1021) from a population-based study were interviewed to assess lifetime grilled-smoked meat intake. SNPs with minor allele frequencies of greater than 0...
November 25, 2016: Annals of Epidemiology
https://www.readbyqxmd.com/read/27924717/effects-of-benzo-a-pyrene-aromatic-amines-and-a-combination-of-both-on-cyp1a1-activities-in-rt-4-human-bladder-papilloma-cells
#18
Sabine Plöttner, Lilian Annika Bastian, Heiko Udo Käfferlein, Thomas Brüning
The interaction of arylamines and polycyclic aromatic hydrocarbons (PAH) is of particular interest in the etiology of bladder cancer. The aim of this study was to (1) examine the metabolic capacity of RT-4 human bladder papilloma cells and (2) investigate the influence of aromatic amines on the induction of cytochrome P-450 1A1 (CYP1A1) activity and their effects on benzo[a]pyrene (BaP)-induced CYP1A1 activities. Cells were incubated for 24 h with different concentrations of BaP, 1- or 2-naphthylamine (NA), 2-, 3-, or 4-aminobiphenyl (ABP), and binary mixtures consisting of 1 µM BaP and different concentrations of each arylamine...
2016: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/27920155/sos2-and-acp1-loci-identified-through-large-scale-exome-chip-analysis-regulate-kidney-development-and-function
#19
Man Li, Yong Li, Olivia Weeks, Vladan Mijatovic, Alexander Teumer, Jennifer E Huffman, Gerard Tromp, Christian Fuchsberger, Mathias Gorski, Leo-Pekka Lyytikäinen, Teresa Nutile, Sanaz Sedaghat, Rossella Sorice, Adrienne Tin, Qiong Yang, Tarunveer S Ahluwalia, Dan E Arking, Nathan A Bihlmeyer, Carsten A Böger, Robert J Carroll, Daniel I Chasman, Marilyn C Cornelis, Abbas Dehghan, Jessica D Faul, Mary F Feitosa, Giovanni Gambaro, Paolo Gasparini, Franco Giulianini, Iris Heid, Jinyan Huang, Medea Imboden, Anne U Jackson, Janina Jeff, Min A Jhun, Ronit Katz, Annette Kifley, Tuomas O Kilpeläinen, Ashish Kumar, Markku Laakso, Ruifang Li-Gao, Kurt Lohman, Yingchang Lu, Reedik Mägi, Giovanni Malerba, Evelin Mihailov, Karen L Mohlke, Dennis O Mook-Kanamori, Antonietta Robino, Douglas Ruderfer, Erika Salvi, Ursula M Schick, Christina-Alexandra Schulz, Albert V Smith, Jennifer A Smith, Michela Traglia, Laura M Yerges-Armstrong, Wei Zhao, Mark O Goodarzi, Aldi T Kraja, Chunyu Liu, Jennifer Wessel, Eric Boerwinkle, Ingrid B Borecki, Jette Bork-Jensen, Erwin P Bottinger, Daniele Braga, Ivan Brandslund, Jennifer A Brody, Archie Campbell, David J Carey, Cramer Christensen, Josef Coresh, Errol Crook, Gary C Curhan, Daniele Cusi, Ian H de Boer, Aiko P J de Vries, Joshua C Denny, Olivier Devuyst, Albert W Dreisbach, Karlhans Endlich, Tõnu Esko, Oscar H Franco, Tibor Fulop, Glenn S Gerhard, Charlotte Glümer, Omri Gottesman, Niels Grarup, Vilmundur Gudnason, Tamara B Harris, Caroline Hayward, Lynne Hocking, Albert Hofman, Frank B Hu, Lise Lotte N Husemoen, Rebecca D Jackson, Torben Jørgensen, Marit E Jørgensen, Mika Kähönen, Sharon L R Kardia, Wolfgang König, Charles Kooperberg, Jennifer Kriebel, Lenore J Launer, Torsten Lauritzen, Terho Lehtimäki, Daniel Levy, Pamela Linksted, Allan Linneberg, Yongmei Liu, Ruth J F Loos, Antonio Lupo, Christine Meisinger, Olle Melander, Andres Metspalu, Paul Mitchell, Matthias Nauck, Peter Nürnberg, Marju Orho-Melander, Afshin Parsa, Oluf Pedersen, Annette Peters, Ulrike Peters, Ozren Polasek, David Porteous, Nicole M Probst-Hensch, Bruce M Psaty, Lu Qi, Olli T Raitakari, Alex P Reiner, Rainer Rettig, Paul M Ridker, Fernando Rivadeneira, Jacques E Rossouw, Frank Schmidt, David Siscovick, Nicole Soranzo, Konstantin Strauch, Daniela Toniolo, Stephen T Turner, André G Uitterlinden, Sheila Ulivi, Dinesh Velayutham, Uwe Völker, Henry Völzke, Melanie Waldenberger, Jie Jin Wang, David R Weir, Daniel Witte, Helena Kuivaniemi, Caroline S Fox, Nora Franceschini, Wolfram Goessling, Anna Köttgen, Audrey Y Chu
Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3...
December 5, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27916218/fenofibrate-attenuates-malignant-hypertension-by-suppression-of-the-renin-angiotensin-system-a-study-in-cyp1a1-ren-2-transgenic-rats
#20
Šárka Jíchová, Šárka Doleželová, Libor Kopkan, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka
BACKGROUND: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II)-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. METHODS: Malignant hypertension was induced by 12 days׳ dietary administration of 0...
December 2016: American Journal of the Medical Sciences
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