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https://www.readbyqxmd.com/read/28443179/inhibition-of-carcinogen-activating-cytochrome-p450-enzymes-by-xenobiotic-chemicals-in-relation-to-antimutagenicity-and-anticarcinogenicity
#1
REVIEW
Tsutomu Shimada
A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), aryl- and heterocyclic amines and tobacco related nitrosamines, are ubiquitous environmental carcinogens and are required to be activated to chemically reactive metabolites by xenobiotic-metabolizing enzymes, including cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of various human P450 enzymes determined to date, CYP1A1, 1A2, 1B1, 2A13, 2A6, 2E1, and 3A4 are reported to play critical roles in the bioactivation of these carcinogenic chemicals...
April 2017: Toxicological Research
https://www.readbyqxmd.com/read/28441709/association-of-cyp3a5-3-and-cyp1a1-2c-polymorphism-with-development-of-acute-myeloid-leukemia-in-egyptian-patients
#2
Nahed Abd El Wahab, Nevine F Shafik, Roxan E Shafik, Sherin A Taha, Hanan E Shafik, Amira D Darwish
Aim: Cytochrome P450 (CYP) enzyme catalyzes the phase I metabolism reaction which metabolize endogenous and exogenous DNA-reactive chemical compounds and xenobiotics which could induce genotoxicity and increase the risk for leukemia. We aimed to detect frequency of CYP3A5*3 and CYP1A1*2C polymorphisms in Egyptian acute myeloid leukemia (AML) patients and to determine role of allele’s variants as a risk factor for developing leukemia. Patients and Methods: A case-control study was conducted on seventy acute myeloid leukemia patients and thirty control subjects...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28437180/a-novel-drug-induced-hybrid-electrospun-pcl-cell-derived-ecm-scaffold-for-liver-tissue-engineering
#3
Rhiannon Grant, David Hay, Anthony Callanan
Liver transplant is the only treatment option for patients with end-stage liver failure, however there are too few donor livers available for transplant. Whole organ tissue engineering presents a potential solution to the problem of rapidly escalating donor liver shortages world-wide. A major challenge for liver tissue engineers is the creation of a hepatocyte micro-environment; a niche in which liver cells can survive and function optimally. While polymers and decellularized tissues pose an attractive option for scaffold manufacturing, neither alone has thus far proved sufficient...
February 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28434254/association-of-gstt1-null-xpd-751%C3%A2-cc-and-xpc-939%C3%A2-cc-genotypes-with-increased-levels-of-genomic-damage-among-hospital-pathologists
#4
Alfredo Santovito, Marta Delsoglio, Eleonora Manitta, Giulia Picco, Giulia Meschiati, Michela Chiarizio, Claudio Gendusa, Piero Cervella
CONTEXT: Hospital workers are at risk for genotoxic damage following occupationally exposure to xenobiotics. Pathologists are exposed to chemicals during their use in health care environments, particularly throughout inhalation of airborne agents, absorption through skin or contact with the patient's body fluids. OBJECTIVE: We evaluated the level of genomic damage in a sample of 61 hospital pathologists (occupationally exposed to antineoplastic drugs and sterilizing agents) and 60 control subjects...
April 24, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/28433806/polymorphism-of-cyp1a1-gene-variants-rs4646903-and-rs1048943-relation-to-the-incidence-of-cervical-cancer-in-chhattisgarh
#5
Vijaylakshmi Jain, Yashwant K Ratre, Dnyanesh Amle, Pankaj K Mishra, Pradeep K Patra
Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls)...
April 13, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28433708/toxicological-characterisation-of-two-novel-selective-aryl-hydrocarbon-receptor-modulators-in-sprague-dawley-rats
#6
Selma Mahiout, Jere Lindén, Javier Esteban, Ismael Sánchez-Pérez, Satu Sankari, Lars Pettersson, Helen Håkansson, Raimo Pohjanvirta
The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28433593/tissue-distribution-and-metabolism-of-triadimefon-and-triadimenol-enantiomers-in-chinese-lizards-eremias-argus
#7
Jitong Li, Yinghuan Wang, Wei Li, Peng Xu, Baoyuan Guo, Jianzhong Li, Huili Wang
Triadimefon (TF, S-(+)-TF, R-(-)-TF) and its metabolite triadimenol (TN, TN-A1, A2 and TN-B1, B2) are two systemic fungicides and both of them are chiral pharmaceuticals which are widely used in agricultural industry. Many researches focused on the toxicity effects of triadimefon on mammals, while the ecotoxicological data of tiradimefon on reptiles is limited. In order to understand the toxicity mechanism of triadimefon in reptiles, the current study administrated S-(+)-TF or R-(-)-TF traidimefon (50mg/kg(bw)) to Chinese lizards (Eremias argus) respectively, the absorption, distribution of triadimefon and the formation of triadimenol were analysed at different sampling times...
April 20, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28428138/pregnane-x-receptor-regulates-the-ahr-cyp1a1-pathway-and-protects-liver-cells-from-benzo-%C3%AE-pyrene-induced-dna-damage
#8
Hongmei Cui, Xinsheng Gu, Jingshu Chen, Ying Xie, Sui Ke, Jing Wu, Andrei Golovko, Benjamin Morpurgo, Chunhong Yan, Timothy D Phillips, Wen Xie, Jianyuan Luo, Zhijun Zhou, Yanan Tian
Pregnane X receptor (PXR) plays an important role in protecting cells from mutagenic DNA damages induced by endogenous and exogenous toxicants. This protective function is often attributed to the PXR-regulated metabolic detoxification. Here we report a novel potential mechanism that PXR reduces benzo-[α]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the bioactivation of BaP. We have utilized three well-characterized cell lines, i...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28425455/the-effect-of-hydraulic-flowback-and-produced-water-on-gill-morphology-oxidative-stress-and-antioxidant-response-in-rainbow-trout-oncorhynchus-mykiss
#9
Tamzin A Blewett, Alyssa M Weinrauch, Perrine L M Delompré, Greg G Goss
Hydraulic fracturing fluid are complex mixtures containing high concentrations of salts (up to 330,000 ppm), organic, and metal contaminants. However, little data exist on the potential mechanisms of toxicity of these flowback and produced wastewaters (FPW) on aquatic biota. Juvenile rainbow trout were exposed to either control, FPW (2.5 or 7.5%), FPW that had been treated with activated charcoal (AC), or a custom salt-matched control (SW; replicating only the salt content of FPW) for 48 hours. Gill histology revealed decreases in interlamellar cell mass (ILCM) and mean lamellar length in all treatments (FPW, AC and SW) compared to control, indicative of hyperosmotic stress...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425245/xenobiotic-drug-metabolizing-enzyme-and-tp53-polymorphisms-and-clinical-outcome-in-advanced-nonsmall-cell-lung-cancer-patients
#10
Volkan Karacaoğlan, Ahmet Oğuz Ada, Serdar Bilgen, Guzide Tuğba Çetinkaya, Emre Soydaş, Celalettin Semih Kunak, Sibel Meryem Alpar, Meral Gülhan, Mümtaz Işcan
BACKGROUND/AIM: The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated. MATERIALS AND METHODS: Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP)...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28415751/gene-gene-interaction-between-pparg-and-cyp1a1-gene-on-coronary-artery-disease-in-the-chinese-han-population
#11
Xiaojiang Zhang, Shuzheng Lv, Chengjun Guo, Conghong Shi, Yunpeng Chi, Lin Zhao, Guozhong Wang, Zhisheng Wang
AIMS: To observe the influence of the peroxisome proliferator-activator receptor-G (PPAR-G) gene and cytochrome P4501A1 (CYP1A1) single-nucleotide polymorphisms (SNPs), and interactions among several SNPs on coronary artery disease (CAD) risk. METHODS: A total of 1106 participants (including 583 males and 523 females) including 550 CAD patients and 556 control subjects were recruited in this study, and the mean age for these participants was 55.5 ± 11.8 years old...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412920/neuropsychiatric-and-general-interactions-of-natural-and-synthetic-cannabinoids-with-drugs-of-abuse-and-medicines
#12
Ana Lucia Arellano, Esther Papaseit, Anna Romaguera, Marta Torrens, Magi Farré
Cannabis is the most widely used illicit drug. The two most important natural cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The THC content of cannabis has been increasing during the last years and recently appeared in the market a series of synthetic cannabinoids with potent agonist activity. Recreational users frequently combine cannabis with other drugs of abuse as alcohol, amphetamines and derivatives, nicotine and cocaine. In addition these subjects can be taking medicines for acute and chronic medical conditions...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28412649/proinflammatory-effects-of-diesel-exhaust-particles-from-moderate-blend-concentrations-of-1st-and-2nd-generation-biodiesel-in-beas-2b-bronchial-epithelial-cells-the-fuelhealth-project
#13
Tonje S Skuland, Magne Refsnes, Pål Magnusson, Michał Oczkowski, Joanna Gromadzka-Ostrowska, Marcin Kruszewski, Remigiusz Mruk, Oddvar Myhre, Anna Lankoff, Johan Øvrevik
Biodiesel fuel fuels are introduced at an increasing extent as a more carbon-neutral alternative to reduce CO2-emissions, compared to conventional diesel fuel. In the present study we have investigated the impact of increasing the use of 1st generation fatty acid methyl ester (FAME) biodiesel from current 7% blend (B7) to 20% blend (B20), or by increasing the biodiesel content by adding 2nd generation hydrotreated vegetable oil (HVO) based biodiesel (SHB; Synthetic Hydrocarbon Biofuel) on toxicity of diesel exhaust particles (DEP) in an in vitro system...
April 5, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28405246/modulation-of-benzo-a-pyrene-dna-adduct-formation-by-cyp1-inducer-and-inhibitor
#14
REVIEW
Kazuhiro Shiizaki, Masanobu Kawanishi, Takashi Yagi
Benzo[a]pyrene (BaP) is a well-studied pro-carcinogen that is metabolically activated by cytochrome P450 enzymes. Cytochrome P4501A1 (CYP1A1) has been considered to play a central role in the activation step, which is essential for the formation of DNA adducts. This enzyme is strongly induced by many different chemical agents, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which binds to the aryl hydrocarbon receptor (AhR). Therefore, AhR activators are suspected to have the potential to aggravate the toxicity of BaP through the induction of CYP1A1...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28403117/association-of-the-ace-gstm1-il-6-nos3-and-cyp1a1-polymorphisms-with-susceptibility-of-mycoplasma-pneumoniae-pneumonia-in-chinese-children
#15
Jie Zhao, Wen Zhang, Li Shen, Xiaomeng Yang, Yi Liu, Zhongtao Gai
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) and the clinical presentation of mycoplasma pneumoniae pneumonia (MPP) varies widely. Genetic variability affecting the host response may also influence the susceptibility to MPP. Several studies have investigated the association between single nucleotide polymorphism (SNP) of some genes and the risks of CAP; however, the results were inconsistent. Here, we investigated the association of 5 functional genes and the risks of MPP, including ACE (rs4340), GSTM1 (Ins/del), IL-6 (rs1800795), NOS3 (rs1799983), and CYP1A1 (rs2606345) in a total of 715 subjects (415 cases, 300 controls) by using tetra-primer allele-specific polymerase chain reaction (PCR) and Sanger sequencing...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28400261/involvement-of-astrocytic-cyp1a1-isoform-in-the-metabolism-and-toxicity-of-the-alkaloid-pyrrolizidine-monocrotaline
#16
Ravena P Nascimento, Joana L Oliveira, José Leilton C Carvalho, William A Santos, Thyago Rubens C Pires, Maria José M Batatinha, Ramon S El-Bachá, Victor Diógenes A Silva, Silvia L Costa
Monocrotaline (MCT) and its pyrrole derivative, dehydromonocrotaline (DHMC), interact with molecular targets in cells of the central nervous system. DHMC presents higher toxicity than MCT indicating that its metabolism of MCT is a critical step of this alkaloid toxicity. This study sought to elucidate the metabolism and the toxicity of MCT in C6 astrocyte cell line and primary cultures of rat astrocytes by investigating metabolic enzymatic mechanisms of the cytochrome P450 (CYP) system and conjugation with glutathione...
April 8, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28393180/fenofibrate-inhibits-tumour-intravasation-by-several-independent-mechanisms-in-a-3-dimensional-co-culture-model
#17
Chi Huu Nguyen, Nicole Huttary, Atanas G Atanasov, Waranya Chatuphonprasert, Stefan Brenner, Adryan Fristiohady, Junli Hong, Serena Stadler, Silvio Holzner, Daniela Milovanovic, Verena M Dirsch, Brigitte Kopp, Philipp Saiko, Liselotte Krenn, Walter Jäger, Georg Krupitza
Lymph node metastasis of breast cancer is a clinical marker of poor prognosis. Yet, there exist no therapies targeting mechanisms of intravasation into lymphatics. Herein we report on an effect of the antidyslipidemic drug fenofibrate with vasoprotective activity, which attenuates breast cancer intravasation in vitro, and describe the potential mechanisms. To measure intravasation in a 3-dimensional co-culture model MDA-MB231 and MCF-7 breast cancer spheroids were placed on immortalised lymphendothelial cell (LEC) monolayers...
April 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28390928/itraconazole-cis-diastereoisomers-activate-aryl-hydrocarbon-receptor-ahr-and-pregnane-x-receptor-pxr-and-induce-cyp1a1-in-human-cell-lines-and-human-hepatocytes
#18
Martina Stepankova, Barbora Pastorkova, Petr Bachleda, Zdenek Dvorak
Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR...
April 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28390242/cyp1a-protein-expression-and-catalytic-activity-in-double-crested-cormorants-experimentally-exposed-to-deepwater-horizon-mississippi-canyon-252-oil
#19
Courtney R Alexander, Michael J Hooper, Dave Cacela, Kim D Smelker, Caleshia S Calvin, Karen M Dean, Steve J Bursian, Fred L Cunningham, Katie C Hanson-Dorr, Katherine E Horak, John P Isanhart, Jane Link, Susan A Shriner, Céline A J Godard-Codding
Double-crested cormorants (Phalacrocorax auritus, DCCO) were orally exposed to Deepwater Horizon Mississippi Canyon 252 (DWH) oil to investigate oil-induced toxicological impacts. Livers were collected for multiple analyses including cytochrome P4501A (CYP1A) enzymatic activity and protein expression. CYP1A enzymatic activity was measured by alkoxyresorufin O-dealkylase (AROD) assays. Activities specific to the O-dealkylation of four resorufin ethers are reported: benzyloxyresorufin O-debenzylase (BROD), ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and pentoxyresorufin O-depentylase (PROD)...
April 5, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28384415/down-regulation-of-cytochrome-p450-2c8-by-3-methylcholanthrene-in-human-hepatocellular-carcinoma-cell-lines
#20
Rucha Utgikar, David S Riddick
The marked induction of cytochromes P450 such as CYP1A1 caused by polycyclic aromatic hydrocarbons (PAHs) like 3-methylcholanthrene (MC) is often accompanied by suppression of other hepatic P450s. The molecular mechanisms, functional consequences, and human relevance of P450 down-regulation by PAHs are poorly understood. MC suppresses mRNA levels for CYP2C8, an important human P450, in cultured human hepatocytes. To avoid hepatocyte lot-to-lot variability, we assessed <i>CYP2C8</i> regulation by MC in HepaRG cells, a terminally differentiated human hepatocellular carcinoma cell line that maintains high P450 expression...
April 6, 2017: Canadian Journal of Physiology and Pharmacology
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