cytochrome p 450 cyp1a2

Summary

Summary: A cytochrome P-450 monooxygenase that can be induced by polycyclic aromatic xenobiotics in the liver of human and several animal species. This enzyme is of significant clinical interest due to the large number of drug interactions associated with its induction and its metabolism of THEOPHYLLINE. Caffeine is considered to be a model substrate for this enzyme. CYP1A2 activity can also be increased by environmental factors such as cigarette smoking, charbroiled meat, cruciferous vegetables, and a number of drugs including phenytoin, phenobarbital, and omeprazole.

Top Publications

  1. ncbi A distribution study of CYP1A2 phenotypes among smokers and non-smokers in a cohort of healthy Caucasian volunteers
    D Schrenk
    Institute of Toxicology, University of Tubingen, Germany
    Eur J Clin Pharmacol 53:361-7. 1998
  2. ncbi Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations
    O V Olesen
    Department of Biological Psychiatry, Psychiatric University Hospital, Risskov, Denmark
    J Clin Pharmacol 41:823-32. 2001
  3. ncbi Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9
    Yoko Otake
    Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Drug Metab Dispos 30:103-5. 2002
  4. ncbi Antisense strategies for redirection of drug metabolism: using paclitaxel as a model
    Vikram Arora
    Research and Development, AVI BioPharma, Corvallis, OR, USA
    Methods Mol Med 106:273-92. 2005
  5. ncbi The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis
    Daniel W Nebert
    Department of Environmental Health, and Center for Environmental Genetics, University of Cincinnati Medical Center, P O Box 670056, Cincinnati, Ohio 45267 0056, USA
    Nat Rev Cancer 6:947-60. 2006
  6. ncbi Role of polymorphic human cytochrome P450 enzymes in estrone oxidation
    Alastair E Cribb
    Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, 550 University Avenue, Charlottetown, Prince Edward Island, Canada C1A 4P3
    Cancer Epidemiol Biomarkers Prev 15:551-8. 2006
  7. ncbi Cytochromes P450 and metabolism of xenobiotics
    P Anzenbacher
    Institute of Pharmacology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic
    Cell Mol Life Sci 58:737-47. 2001
  8. ncbi Coffee consumption and CYP1A2*1F genotype modify age at breast cancer diagnosis and estrogen receptor status
    Erika Bågeman
    Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
    Cancer Epidemiol Biomarkers Prev 17:895-901. 2008
  9. pmc Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism
    Christoph Sachse
    Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK
    Br J Clin Pharmacol 55:68-76. 2003
  10. pmc The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women
    Anna Nordmark
    Department of Medical Laboratory Science and Technology, Division of Clinical Pharmacology, Karolinska Institutet, C 168, Huddinge University Hospital, SE 141 86 Stockholm, Sweden
    Br J Clin Pharmacol 54:504-10. 2002

Research Grants

  1. CYP1A1 GENE AND ENVIRONMENTAL TOXICITY
    Daniel Nebert; Fiscal Year: 2005
  2. Interplay between metabolism and FXR activation in scoparone signaling
    Bingfang Yan; Fiscal Year: 2013
  3. Genetic Susceptibility to PCB-induced Motor Dysfunction
    CHRISTINE PERDAN CURRAN; Fiscal Year: 2012
  4. ACTIVITY OF P450/1A2 AND 3A4 AND BREAST CANCER RISK
    Wei Zheng; Fiscal Year: 1999
  5. Glutathione in Environmental Toxicity and Disease
    HOWARD SHERTZER; Fiscal Year: 2007
  6. RECEPTOR MEDIATED OXIDATIVE STRESS
    HOWARD SHERTZER; Fiscal Year: 2003
  7. MECHANISM OF PORPHYRIA CAUSED BY TCDD
    Peter Sinclair; Fiscal Year: 2002
  8. ETHANOL EFFECTS ON BONE FORMATION IN PREGNANCY
    Martin Ronis; Fiscal Year: 2006
  9. PAHs: Balance of Detoxication vs Metabolic Activation
    Daniel Nebert; Fiscal Year: 2009
  10. Molecular Genetics of Cadmium Toxicity
    Daniel W Nebert; Fiscal Year: 2010

Detail Information

Publications237 found, 100 shown here

  1. ncbi A distribution study of CYP1A2 phenotypes among smokers and non-smokers in a cohort of healthy Caucasian volunteers
    D Schrenk
    Institute of Toxicology, University of Tubingen, Germany
    Eur J Clin Pharmacol 53:361-7. 1998
    ....
  2. ncbi Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations
    O V Olesen
    Department of Biological Psychiatry, Psychiatric University Hospital, Risskov, Denmark
    J Clin Pharmacol 41:823-32. 2001
    ..The rate of other metabolic routes mediated by CYP2D6 only corresponded to about one fifth of the CYP2D6 catalyzed N-demethylation rate...
  3. ncbi Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9
    Yoko Otake
    Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Drug Metab Dispos 30:103-5. 2002
    ..In addition, CYP1A1, although less efficient, was also able to oxidize the two flavonols. Thus, dietary flavonols are likely to undergo oxidative metabolism mainly in the liver but also extrahepatically...
  4. ncbi Antisense strategies for redirection of drug metabolism: using paclitaxel as a model
    Vikram Arora
    Research and Development, AVI BioPharma, Corvallis, OR, USA
    Methods Mol Med 106:273-92. 2005
  5. ncbi The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis
    Daniel W Nebert
    Department of Environmental Health, and Center for Environmental Genetics, University of Cincinnati Medical Center, P O Box 670056, Cincinnati, Ohio 45267 0056, USA
    Nat Rev Cancer 6:947-60. 2006
    ..We suggest a two-tiered system to predict an overall inter-individual risk of tumorigenesis based on DNA variants in certain 'early defence' CYP genes, combined with polymorphisms in various downstream target genes...
  6. ncbi Role of polymorphic human cytochrome P450 enzymes in estrone oxidation
    Alastair E Cribb
    Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, 550 University Avenue, Charlottetown, Prince Edward Island, Canada C1A 4P3
    Cancer Epidemiol Biomarkers Prev 15:551-8. 2006
    ..These enzymes are all known to be genetically variant in the human population, and additional studies to assess the role CYP1A2, CYP2C19, and CYP3A5 in breast cancer risk are indicated...
  7. ncbi Cytochromes P450 and metabolism of xenobiotics
    P Anzenbacher
    Institute of Pharmacology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic
    Cell Mol Life Sci 58:737-47. 2001
    ..Genetically dependent variabilities of individual P450 activities and levels are described, documenting the importance of pharmacogenetics aimed at explaining differences in the response of the organism to various drugs...
  8. ncbi Coffee consumption and CYP1A2*1F genotype modify age at breast cancer diagnosis and estrogen receptor status
    Erika Bågeman
    Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
    Cancer Epidemiol Biomarkers Prev 17:895-901. 2008
    ..2; 95% confidence interval, 1.9-9.3; P = 0.0002). These findings raise the hypothesis that coffee slows the growth of ER-positive tumors in patients with CYP1A2*1F A/A and may have implications for breast cancer if confirmed...
  9. pmc Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism
    Christoph Sachse
    Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK
    Br J Clin Pharmacol 55:68-76. 2003
    ..Several single nucleotide polymorphisms (SNPs) of the cytochrome P450 enzyme 1A2 gene (CYP1A2) have been reported. Here, frequencies, linkage disequilibrium and phenotypic consequences of six SNPs are described...
  10. pmc The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women
    Anna Nordmark
    Department of Medical Laboratory Science and Technology, Division of Clinical Pharmacology, Karolinska Institutet, C 168, Huddinge University Hospital, SE 141 86 Stockholm, Sweden
    Br J Clin Pharmacol 54:504-10. 2002
    ..To investigate the influence of the CYP1A2*1F mutation on CYP1A2 activity in smoking and nonsmoking pregnant women...
  11. ncbi Differential time-course and dose-response relationships of TCDD-induced CYP1B1, CYP1A1, and CYP1A2 proteins in rats
    M J Santostefano
    Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599 7270, USA
    Biochem Biophys Res Commun 233:20-4. 1997
    ..This study demonstrates that TCDD exhibits differential dose-response and time-course relationships on hepatic localization and cytochrome P-450 protein expression...
  12. ncbi Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy
    Keiji Takata
    Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Science, Kumamoto University, and Department of Medicine, Kumamoto City Hospital, Japan
    Eur J Clin Pharmacol 62:23-8. 2006
    ....
  13. pmc Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer
    Donghui Li
    Department of Gastrointestinal Medical Oncology, The University of Texas, M D Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, TX 77030, USA
    Carcinogenesis 27:103-11. 2006
    ..9, 95% CI: 1.2-6.9) and among females (AOR: 2.5, 95% CI: 1.1-5.7). These data suggest that polymorphisms of the CYP1A2 and NAT1 genes modify the risk of pancreatic cancer...
  14. ncbi Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid-DNA adducts found in patients with urothelial cancer
    Marie Stiborova
    Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
    Int J Cancer 113:189-97. 2005
    ..In addition, prostaglandin H synthase is another enzyme activating AAI in renal microsomes. The results demonstrate for the first time the potential of microsomal enzymes in human liver and kidney to activate AAI by nitroreduction...
  15. ncbi Human enzymes involved in the metabolic activation of carcinogenic aristolochic acids: evidence for reductive activation by cytochromes P450 1A1 and 1A2
    M Stiborova
    Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, The Czech Republic
    Chem Res Toxicol 14:1128-37. 2001
    ..These results are the first report on the activation of AA by human enzymes and clearly demonstrate the role of P450 1A1, 1A2, and NADPH:P450 reductase in catalyzing the reductive activation of AA...
  16. pmc Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines
    M A Butler
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079
    Proc Natl Acad Sci U S A 86:7696-700. 1989
    ....
  17. ncbi Impairment of human CYP1A2-mediated xenobiotic metabolism by Antley-Bixler syndrome variants of cytochrome P450 oxidoreductase
    Michel Kranendonk
    Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349 008 Lisbon, Portugal
    Arch Biochem Biophys 475:93-9. 2008
    ....
  18. ncbi The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors
    Birgitte B Rasmussen
    Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark
    Pharmacogenetics 12:473-8. 2002
    ..725 (95% confidence interval 0.577-0.822). Unique environmental effects seem to account for the remainder 0.275 (95% confidence interval, 0.178-0.423). Our study shows that the CYP1A2 activity is mainly governed by genetic factors...
  19. ncbi The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers
    Joanne Kotsopoulos
    Centre for Research in Women s Health, Women s College Hospital, University of Toronto, Canada
    Cancer Epidemiol Biomarkers Prev 16:912-6. 2007
    ..This study suggests that caffeine protects against breast cancer in women with a BRCA1 mutation and illustrates the importance of integrating individual genetic variability when assessing diet-disease associations...
  20. ncbi Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms
    Anthony J Lee
    Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina 29208, USA
    Endocrinology 144:3382-98. 2003
    ..In conclusion, many human CYP isoforms are involved in the oxidative metabolism of 17beta-estradiol and estrone, with a varying degree of catalytic activity and distinct regioselectivity...
  21. ncbi 3-Methylcholanthrene elicits DNA adduct formation in the CYP1A1 promoter region and attenuates reporter gene expression in rat H4IIE cells
    Bhagavatula Moorthy
    Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    Biochem Biophys Res Commun 354:1071-7. 2007
    ..Our results suggest that CYP1A2 plays a key role in sequence-specific MC-DNA adduct formation in the CYP1A1 promoter region, leading to attenuation of CYP1A1 gene expression...
  22. pmc Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction
    M C Cornelis
    Department of Nutritional Sciences, University of Toronto, Ontario, Canada M5S 3E2
    J Med Genet 41:758-62. 2004
    ..The objective of this study was to determine the effects of CYP1A1 and CYP1A2 genotypes on risk of myocardial infarction (MI) and whether smoking interacts with genotype to modify risk...
  23. ncbi Influence of the genetic polymorphism in the 5'-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers
    Sofia Pavanello
    Occupational Health Section, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, Padova 35128, Italy
    Mutat Res 587:59-66. 2005
    ..This information is of interest for future studies assessing the possible role of tobacco smoke-inducible CYP1A2 genotypes as individual susceptibility factors in exposure to carcinogens...
  24. ncbi Effects of CYP1A2 on disposition of 2,3,7, 8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, and 2,2',4,4',5,5'-hexachlorobiphenyl in CYP1A2 knockout and parental (C57BL/6N and 129/Sv) strains of mice
    J J Diliberto
    National Health Effects and Environmental Research Laboratory, U S Environmental Protection Agency, Research Triangle Park, North Carolina, 27711, USA
    Toxicol Appl Pharmacol 159:52-64. 1999
    ..Another difference between KO mice and parental strains was the enhanced urinary excretion of 4-PeCDF. This study demonstrates the importance of CYP1A2 in pharmacokinetic behavior and mechanistic issues for TCDD and related compounds...
  25. ncbi Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: insights into the measurement of hepatic cytochrome P450 1A2 induction
    Klaus Abraham
    Department of Pediatric Pneumology and Immunology, Institute of Clinical Pharmacology, Charite, Humboldt University Berlin, Augustenburger Platz 1, 13 153 Berlin, Germany
    Clin Pharmacol Ther 72:163-74. 2002
    ..We compared the performance of several modifications of the caffeine test for measurement of CYP1A2 activity in subjects with exceptionally high, low, or absent enzyme induction...
  26. ncbi Estrogen metabolism-related genes and breast cancer risk: the multiethnic cohort study
    Loic Le Marchand
    Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Suite 407, 1236 Lauhala Street, Honolulu, HI 96813, USA
    Cancer Epidemiol Biomarkers Prev 14:1998-2003. 2005
    ..They also provide support for an inverse association between CYP1A2*1F and breast cancer, which is consistent with the observation of lower circulating estrogen levels in premenopausal women with the CC genotype in a previous study...
  27. ncbi Population-based case-control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk
    Ji Rong Long
    Department of Medicine and Vanderbilt Ingram Cancer Center, Vanderbilt University, 1161 21st Avenue South, Nashville, TN 37232, USA
    Pharmacogenet Genomics 16:237-43. 2006
    ....
  28. ncbi An investigation of mammographic density and gene variants in healthy women
    Gertraud Maskarinec
    Cancer Research Center of Hawaii, Honolulu, HI 96813, USA
    Int J Cancer 112:683-8. 2004
    ..Our data suggest lower mammographic density for women carrying the COMT and CYP1A2 variant alleles than for women carrying the common alleles, though this is the opposite of what is commonly hypothesized from the enzyme function...
  29. ncbi Fluorinated 2-(4-amino-3-methylphenyl)benzothiazoles induce CYP1A1 expression, become metabolized, and bind to macromolecules in sensitive human cancer cells
    Eileen Brantley
    Biological Testing Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21701, USA
    Drug Metab Dispos 32:1392-401. 2004
    ..These data are concordant with the antiproliferative activity of fluorinated benzothiazoles deriving from their ability to become metabolized and bind to macromolecules within sensitive cells...
  30. ncbi Association of genetic polymorphisms with serum estrogens measured multiple times during a 2-year period in premenopausal women
    Galina Lurie
    Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Honolulu, Hawaii 96813, USA
    Cancer Epidemiol Biomarkers Prev 14:1521-7. 2005
    ..37 versus 1.76; P = 0.002). These data suggest that CYP1A2*1F is associated with lower circulating levels of E2, and that it may be a susceptibility locus for breast cancer...
  31. ncbi Effect of propiverine on cytochrome P450 enzymes: a cocktail interaction study in healthy volunteers
    D Tomalik-Scharte
    Department of Pharmacology, Clinical Pharmacology, University of Cologne, Gleueler Str 24, 50931 Koln, Germany
    Drug Metab Dispos 33:1859-66. 2005
    ..93-1.00, 0.84-0.96, and 0.97-1.07, respectively). All study drugs were well tolerated. In conclusion, propiverine has a minor potential to cause drug-drug interactions...
  32. ncbi Coffee, CYP1A2 genotype, and risk of myocardial infarction
    Marilyn C Cornelis
    Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
    JAMA 295:1135-41. 2006
    ..Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers...
  33. pmc Cytochrome P450 1A2 (CYP1A2) activity, mammographic density, and oxidative stress: a cross-sectional study
    Chi Chen Hong
    Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Ontario, Canada
    Breast Cancer Res 6:R338-51. 2004
    ..One enzyme that is able to affect both the mitogenic and mutagenic characteristics of estrogens is cytochrome P450 1A2 (CYP1A2), which is principally responsible for the metabolism of 17beta-estradiol...
  34. ncbi Metabolism of the soyabean isoflavone daidzein by CYP1A2 and the extra-hepatic CYPs 1A1 and 1B1 affects biological activity
    Kathryn M Atherton
    Institute for Cell and Molecular Biosciences, University of Newcastle, UK
    Biochem Pharmacol 72:624-31. 2006
    ....
  35. ncbi Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes
    Natasa Djordjevic
    Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, C1 68, SE 14186, Stockholm, Sweden
    Eur J Clin Pharmacol 64:381-5. 2008
    ..To investigate the influence of coffee consumption on CYP1A2 enzyme activity controlling for the effects of smoking and oral contraceptive (OC) use among Serbs and Swedes and to compare CYP1A2 activity between the two populations...
  36. ncbi Metabolic activation of carcinogenic aristolochic acid, a risk factor for Balkan endemic nephropathy
    Marie Stiborova
    Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
    Mutat Res 658:55-67. 2008
    ....
  37. pmc Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort
    Yumie Takata
    Cancer Research Center of Hawaii, 1236 Lauhala Street, Honolulu, HI, USA
    BMC Cancer 7:30. 2007
    ..This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val58 Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort...
  38. ncbi Moderate coffee and alcohol consumption improves the estrogen metabolite profile in adjuvant treated breast cancer patients: a pilot study comparing pre- and post-operative levels
    T L Klug
    Immuna Care Corporation, Bell, PA 19422, USA
    Mol Genet Metab 89:381-9. 2006
    ....
  39. ncbi Regional hepatic CYP1A1 and CYP1A2 induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin evaluated with a multicompartment geometric model of hepatic zonation
    M E Andersen
    ICF Kaiser Engineers, Research Triangle Park, North Carolina 27709, USA
    Toxicol Appl Pharmacol 144:145-55. 1997
    ..No previous model has incorporated regional variations in induction. The PBPK analysis based on the multicompartment liver model suggests that the low-dose behavior for hepatic CYP1A1/CYP1A2 induction by TCDD is highly non-linear...
  40. ncbi Human cytochromes P450 1A1 and 1A2 participate in detoxication of carcinogenic aristolochic acid
    Jana Sistkova
    Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic
    Neuro Endocrinol Lett 29:733-7. 2008
    ..The aim of the study was to resolve which cytochromes P450 (CYP) detoxicate the major component of AA, aristolochic acid I (AAI), to its O-demethylated metabolite, aristolochic acid Ia (AAIa)...
  41. ncbi Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19
    Vishal Agrawal
    Department of Pediatrics, University of California, San Francisco, California 94143 0978, USA
    Pharmacogenet Genomics 18:569-76. 2008
    ..We examined the effects of POR sequence variants on two drug-metabolizing P450 enzymes, CYP1A2 and CYP2C19...
  42. ncbi Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing
    Carsten Skarke
    Pharmazentrum frankfurt ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Eur J Clin Pharmacol 61:887-92. 2005
    ....
  43. ncbi Determination of parameters responsible for pharmacokinetic behavior of TCDD in female Sprague-Dawley rats
    X Wang
    Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599 7270, USA
    Toxicol Appl Pharmacol 147:151-68. 1997
    ..In addition, this study demonstrated some critical issues in PBPK modeling...
  44. ncbi A pharmacodynamic analysis of TCDD-induced cytochrome P450 gene expression in multiple tissues: dose- and time-dependent effects
    M J Santostefano
    Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599 7270, USA
    Toxicol Appl Pharmacol 151:294-310. 1998
    ....
  45. ncbi Subchronic Exposure of [3H]- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female B6C3F1 mice: relationship of steady-state levels to disposition and metabolism
    J J Diliberto
    U S Environmental Protection Agency, ORD, NHEERL, ETD, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 61:241-55. 2001
    ..In addition, this study emphasizes cumulative effects of daily dosing and suggests the importance of tissue dosimetry or body burden for a persistent chemical such as TCDD...
  46. ncbi Oxidative DNA damage in vivo: relationship to age, plasma antioxidants, drug metabolism, glutathione-S-transferase activity and urinary creatinine excretion
    H E Poulsen
    Department of Clinical Pharmacology, Rigshospitalet, University Hospital Copenhagen, Denmark
    Free Radic Res 29:565-71. 1998
    ..50, p < 0.05). We conclude that 8-oxodG excretion is determined by factors like oxygen consumption and CYP1A2 activity rather than by factors like plasma antioxidant concentrations...
  47. ncbi Characterization of the dose-response of CYP1B1, CYP1A1, and CYP1A2 in the liver of female Sprague-Dawley rats following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
    N J Walker
    National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
    Toxicol Appl Pharmacol 154:279-86. 1999
    ....
  48. ncbi Intrinsic hepatic phenotype associated with the Cyp1a2 gene as shown by cDNA expression microarray analysis of the knockout mouse
    Andrew G Smith
    MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicester, United Kingdom
    EHP Toxicogenomics 111:45-51. 2003
    ..These data suggest that the CYP1A2 enzyme might perform additional hepatic endogenous functions heretofore not appreciated...
  49. ncbi Bioavailable flavonoids: cytochrome P450-mediated metabolism of methoxyflavones
    U Kristina Walle
    Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, P O Box 250505, Charleston, SC 29425, USA
    Drug Metab Dispos 35:1985-9. 2007
    ..In summary, the rate of oxidative metabolism of methoxylated flavones, mainly involving CYP1A1 and CYP1A2, varied widely, even between compounds with very similar structures...
  50. ncbi How useful is the "cocktail approach" for evaluating human hepatic drug metabolizing capacity using cytochrome P450 phenotyping probes in vivo?
    E Tanaka
    Institute of Community Medicine, University of Tsukuba, Tsukuba shi, Ibaraki ken 305 8575, Japan
    J Clin Pharm Ther 28:157-65. 2003
    ..Despite current limitations, the cocktail method for obtaining information about multiple CYP activities in a single experimental session is likely to be more widely used as a screening or phenotyping method for humans in the future...
  51. ncbi Protection against Trp-P-2 DNA adduct formation in C57bl6 mice by purpurin is accompanied by induction of cytochrome P450
    Tim Marczylo
    Faculty of Pharmaceutical Sciences, Okayama University, Tsushima naka 1 1 1, Okayama 700 8530, Japan
    J Agric Food Chem 51:3334-7. 2003
    ..It is hypothesized that purpurin exhibits chemopreventive potential by inhibiting the cytochrome P450-dependent metabolism of heterocyclic amines to their genotoxic N-hydroxylamines...
  52. ncbi Dose-dependent effect of alpha-tocopherol on activity of xenobiotic metabolizing enzymes in rat liver
    Yu A Sidorova
    Laboratory of Foreign Compounds Biochemistry, Institute of Molecular Biology and Biophysics, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk
    Bull Exp Biol Med 136:38-41. 2003
    ..These results suggest that alpha-tocopherol induced the enzymes of phase I of xenobiotic metabolism, including CYP1 and CYP2 families involved in the metabolism of drugs and procarcinogenes...
  53. ncbi Identification of cytochrome P450 isoforms involved in 1-hydroxylation of pyrene
    Yong Dae Kim
    Department of Environmental Health, University of Occupational and Environmental Health, 1 1 Iseigaoka, Yahatanishi ku, Kitakyushu 807 8555, Japan
    Environ Res 94:262-6. 2004
    ..This suggests that the individual difference of these enzymes must be included in epidemiological studies to evaluate PAH exposure using urinary 1-OHP...
  54. ncbi Aryl hydrocarbon receptor-mediated induction of microsomal drug-metabolizing enzyme activity by indirubin and indigo
    Kazumi Sugihara
    Graduate School of Biomedical Sciences, Hiroshima University, Japan
    Biochem Biophys Res Commun 318:571-8. 2004
    ..Our results suggest that indirubin and indigo act as inducers for cytochrome P450 1A1/2 mediated by AhR in mammals in vivo...
  55. ncbi In vitro effects of tacrolimus on human cytochrome P450
    K Lecointre
    Toxicology Laboratory, C H U de Bicêtre, AP HP 78 rue du General Leclerc, 94270 Kremlin Bicetre, France
    Fundam Clin Pharmacol 16:455-60. 2002
    ..These observations suggest that tacrolimus is unlikely to potentiate the effect of coadministered drugs through inhibition of their metabolism in the liver...
  56. ncbi Optimizing higher throughput methods to assess drug-drug interactions for CYP1A2, CYP2C9, CYP2C19, CYP2D6, rCYP2D6, and CYP3A4 in vitro using a single point IC(50)
    Feng Gao
    Pfizer Global Research and Development, Groton, CT, USA
    J Biomol Screen 7:373-82. 2002
    ..In addition, the algorithmic approach we propose would obviously be applicable for other in vitro bioactivity and therapeutic target enzyme and receptor screens...
  57. ncbi Rat and human liver cytochrome P-450 isoform metabolism of ecteinascidin 743 does not predict gender-dependent toxicity in humans
    Joel M Reid
    Department of Oncology, Division of Developmental Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    Clin Cancer Res 8:2952-62. 2002
    ..Thus, although it is not possible to rule out gender differences in ET743 human toxicities, our data do not predict major gender-dependent differences in the toxicity of ET743 based on metabolism...
  58. ncbi Pomegranate juice effects on cytochrome P450S expression: in vivo studies
    Ana Faria
    Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal
    J Med Food 10:643-9. 2007
    ..Prevention of procarcinogen activation through CYP activity/expression inhibition may be involved in pomegranate juice's effect on tumor initiation, promotion, and progression...
  59. ncbi Polycyclic aromatic hydrocarbon-inducible DNA adducts: evidence by 32P-postlabeling and use of knockout mice for Ah receptor-independent mechanisms of metabolic activation in vivo
    Sudha R Kondraganti
    Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    Int J Cancer 103:5-11. 2003
    ..In conclusion, these results demonstrate the existence of AHR- and CYP1A1-independent mechanisms of PAH metabolic activation in mouse liver, a phenomenon that may have important implications for PAH-mediated carcinogenesis...
  60. ncbi For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential
    Nadine Dragin
    Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267 0056, USA
    J Biol Chem 281:18591-600. 2006
    ..In contrast, neither CYP1A1 nor CYP1B1 appears to play a role in dioxin-mediated teratogenesis...
  61. ncbi Approach to predict the contribution of cytochrome P450 enzymes to drug metabolism in the early drug-discovery stage: the effect of the expression of cytochrome b(5) with recombinant P450 enzymes
    C Emoto
    Department of Pharmacokinetics Dynamics Metabolism, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Japan Inc, Taketoyo, Aichi, Japan
    Xenobiotica 37:986-99. 2007
    ..In addition, recombinant CYP microsomes co-expressed with cytochrome b(5) might be suitable for the prediction of the CL(int) value...
  62. ncbi Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects
    Xiao Ping Chen
    Pharmacogenetics Research Institute, Central South University, Changsha, Hunan 410078, PR China
    Clin Pharmacol Ther 73:264-71. 2003
    ..This study was designed to define the effect of low-dose aspirin administration on the activity of cytochrome P450 (CYP) in normal human subjects...
  63. ncbi Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition
    Jasminder Sahi
    Department of Pharmacokinetics Pharmacodynamics and Metabolism, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
    Drug Metab Dispos 31:439-46. 2003
    ..While only the induction of CYP3A4 by troglitazone has been demonstrated in vivo, these results suggest that other thiazolidinediones may have the potential to cause clinically significant drug interactions at sufficiently high doses...
  64. ncbi Stereoselectivity in the oxidation of bufuralol, a chiral substrate, by human cytochrome P450s
    Shizuo Narimatsu
    Laboratory of Health Chemistry, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan
    Chirality 15:333-9. 2003
    ....
  65. ncbi Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes
    Heng Keang Lim
    Johnson and Johnson Pharmaceutical Research Institute, Preclinical Pharmacokinetics, Preclinical Drug Evaluation, OCD, K 007, 1001 Route 202 North, P O Box 300, Raritan, NJ 08869, USA
    Drug Metab Dispos 33:1211-9. 2005
    ..Comparison of the apparent partition ratios and inactivation clearance data for the three glitazones suggests that the chromane moiety on troglitazone contributes to its greater potency for mechanism-based inactivation...
  66. ncbi Effects of Chinese, Japanese and Western tea on hepatic P450 enzyme activities in rats
    N Niwattisaiwong
    Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
    Drug Metabol Drug Interact 20:43-56. 2004
    ..Further studies are needed to determine whether there is a relationship between the effect of tea on CYP activities and anti-carcinogenesis...
  67. ncbi Relative contributions of the five major human cytochromes P450, 1A2, 2C9, 2C19, 2D6, and 3A4, to the hepatic metabolism of the proteasome inhibitor bortezomib
    Vinita Uttamsingh
    Department of Drug Metabolism and Pharmacokinetics, Drug Safety and Disposition, Millennium Pharmaceuticals, Cambridge, MA 02139, USA
    Drug Metab Dispos 33:1723-8. 2005
    ....
  68. ncbi Utility of long-term cultured human hepatocytes as an in vitro model for cytochrome p450 induction
    Georgina Meneses-Lorente
    Department of Medicinal Chemistry Drug Metabolism Section, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, United Kingdom
    Drug Metab Dispos 35:215-20. 2007
    ..The use of long-term cultured hepatocytes on 96-well plates has proven to be sensitive, robust, and convenient for assessing P450 induction potential of new compound entities during the drug discovery process...
  69. ncbi [Effects of ginkgolides on gene expression of hepatic cytochrome P-450 in rats]
    Xiu fen Yang
    Department of Pharmacology, Faculty of Pharmacy, Guangxi Traditional Chinese Medical College, Nanning 530001, China
    Zhongguo Zhong Yao Za Zhi 30:1009-13. 2005
    ..To observe the effects of ginkgolides on gene expression of hepatic cytochrome P-450 in rats...
  70. ncbi Modulation of rat liver cytochrome P450 by protein restriction assessed by biochemical and bacterial mutagenicity methods [corrected]
    L Cancino-Badías
    CIBIOMED, ICBP Victoria de Girón, Ciudad Habana, Cuba
    Mutagenesis 18:95-100. 2003
    ..However, the mutagenic potency of benzo[a]pyrene was the same (4 revertants/ microg) with S9 derived from rats fed either a 6 or 24% protein diet...
  71. ncbi The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes
    Hsien Tsung Yao
    Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan, ROC
    Life Sci 79:2432-40. 2006
    ..These results indicate that the PUFAs are potent inhibitors as well as the substrates of CYP2C9 and CYP2C19...
  72. ncbi Effect of a newly developed ketolide antibiotic, telithromycin, on metabolism of theophylline and expression of cytochrome P450 in rats
    Hiroyuki Nosaka
    Department of Medical Technology, Nagoya University School of Health Sciences, Daikominami, Higashi ku, Nagoya 461 8673, Japan
    Life Sci 79:50-6. 2006
    ..The present study suggests that telithromycin at the dose used in this study alters the pharmacokinetics and metabolism of theophylline, due to reductions in the activity and expression of hepatic CYP1A2 and CYP3A2...
  73. pmc An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid
    Thomas M Polasek
    Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Adelaide, Australia
    Br J Clin Pharmacol 61:570-84. 2006
    ..To characterize potential mechanism-based inactivation (MBI) of major human drug-metabolizing cytochromes P450 (CYP) by monoamine oxidase (MAO) inhibitors, including the antitubercular drug isoniazid...
  74. ncbi A mechanism-based integrated pharmacokinetic enzyme model describing the time course and magnitude of phenobarbital-mediated enzyme induction in the rat
    Mats O Magnusson
    Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE 751 24, Uppsala, Sweden
    Pharm Res 23:521-32. 2006
    ....
  75. ncbi Development of a novel cytochrome p450 bioaffinity detection system coupled online to gradient reversed-phase high-performance liquid chromatography
    Jeroen Kool
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands
    J Biomol Screen 10:427-36. 2005
    ..It is concluded that this novel screening technology offers new perspectives for rapid and sensitive screening of individual compounds in mixtures exhibiting affinity for liver microsomal Cyt P450s...
  76. ncbi In vitro metabolism of the calmodulin antagonist DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate) by human liver microsomes: involvement of cytochromes p450 in a
    Shuko Tachibana
    Drug Metabolism and Physicochemistry Research Laboratories, R and D Division, Daiichi Pharmaceutical Co, Ltd, Toky, Japan
    Drug Metab Dispos 33:1628-36. 2005
    ..25-1.7 microM), a mixed competitive and noncompetitive inhibitor of CYP2C19 (Ki 2.4 microM) and a moderate inhibitor of CYP1A2 and 3A4 (Ki 11.4-20.1 microM), suggesting a high possibility for human drug-drug interaction...
  77. ncbi Effect of sulfur dioxide inhalation on CYP1A1 and CYP1A2 in rat liver and lung
    Guohua Qin
    Institute of Environmental Medicine and Toxicology, Shanxi University, Taiyuan 030006, China
    Toxicol Lett 160:34-42. 2005
    ..Reduction of hepatic and pulmonary CYPlAl and lA2 expression during SO2 exposure may be part of an adaptive response by the liver and lung to minimize cell damage...
  78. ncbi Dehydrogenation of indoline by cytochrome P450 enzymes: a novel "aromatase" process
    Hao Sun
    Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112 5820, USA
    J Pharmacol Exp Ther 322:843-51. 2007
    ..The aromatase mechanism does not seem to occur through N-oxidation or dehydration of an alcohol but rather through a formal dehydrogenation pathway...
  79. ncbi Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC-MS/MS analysis
    Ming Yao
    Department of Biotransformation, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, NJ 08543, USA
    J Pharm Biomed Anal 44:211-23. 2007
    ..The high quality and throughput of these assays make them ideally suited for providing information for decision making in late drug discovery and early development and for providing labeling input for new drug registrations...
  80. ncbi Molecular characterization of cytochrome P450 1A1, 1A2, and 1B1, and effects of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners on their hepatic expression in Baikal seal (Pusa sibirica)
    Shusaku Hirakawa
    Center for Marine Environmental Studies, Ehime University, Matsuyama, Japan
    Toxicol Sci 97:318-35. 2007
    ..Furthermore, ratios of CYP1B1/CYP1A1 mRNA expression levels increased with TEQs, indicating the enhanced risk of carcinogenicity by preferential induction of CYP1B1 by TEQs in the liver...
  81. ncbi Impaired microsomal oxidation of the atypical antipsychotic agent clozapine in hepatic steatosis
    Wei V Zhang
    Pharmacogenomics and Drug Development Group, Faculty of Pharmacy, University of Sydney, New South Wales, Australia
    J Pharmacol Exp Ther 322:770-7. 2007
    ..Lipid deposition in livers of patients with the metabolic syndrome may necessitate dosage adjustments for toxic drugs, including CLZ...
  82. ncbi Selectivity of 7-alkoxycoumarins as probe substrates for rat hepatic cytochrome P450 forms is influenced by the substitution pattern on the coumarin nucleus
    J R Fry
    School of Biomedical Sciences, Medical School, Queen s Medical Centre, Nottingham NG7 2UH, UK
    Xenobiotica 34:707-22. 2004
    ....
  83. ncbi Inhibition of human cytochrome P450 enzymes by the natural hepatotoxin safrole
    Yune Fang Ueng
    National Research Institute of Chinese Medicine, 155 1, Li Nong Street, Sec 2, Taipei 112, Taiwan, ROC
    Food Chem Toxicol 43:707-12. 2005
    ..These results revealed that safrole was a potent inhibitor of human CYP1A2, CYP2A6, and CYP2E1. With relatively less potency, CYP2D6 and CYP3A4 were also inhibited...
  84. ncbi Metabolic enzyme induction by HepG2 cells exposed to oxygenated and nonoxygenated polycyclic aromatic hydrocarbons
    Kentaro Misaki
    Department of Environmental Engineering and Graduate School of Global Environmental Studies, Kyoto University, Yoshidahonmachi, Kyoto 606 8501, Japan
    Chem Res Toxicol 20:277-83. 2007
    ..Both chemical-dependent and time-dependent induction patterns of NQO1 mRNA were of the mixed types of P4501A1 and AKR1C1. The tendency for the decrease of GSTM1 mRNA was observed when exposed to PAHs B[a]P and B[k]FA...
  85. ncbi Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers
    Rosa F Yeh
    School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA
    J Acquir Immune Defic Syndr 42:52-60. 2006
    ....
  86. ncbi Decreased hepatic drug metabolising enzyme activity in rats with nitrosamine-induced tumours
    P P Maliakal
    School of Pharmacy, University of Otago, Dunedin, New Zealand
    Drug Metabol Drug Interact 19:13-27. 2002
    ..Alteration of the activities of drug metabolising enzymes in rats with chemically induced tumours could be an important factor in determining resistance or susceptibility to xenobiotics and antitumour drugs...
  87. ncbi Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6 and CYP1B1 based on sequence homology with CYP102
    D F Lewis
    Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK
    Toxicology 139:53-79. 1999
    ....
  88. ncbi Effect of alachlor on hepatic cytochrome P450 enzymes in rats
    Nobumitsu Hanioka
    Division of Environmental Chemistry, National Institute of Health Sciences, 1 18 1 Kamiyoga, Setagaya Ku, Tokyo 158 8501, Japan
    Drug Chem Toxicol 25:25-37. 2002
    ..These results suggest that alachlor selectively induces cytochrome P450 isoforms of the CYP1A and CYP2B subfamilies in rat liver microsomes, and that the expression of these isoforms is closely related to the toxicity of alachlor...
  89. ncbi Construction of Salmonella typhimurium YG7108 strains, each coexpressing a form of human cytochrome P450 with NADPH-cytochrome P450 reductase
    K Fujita
    Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    Environ Mol Mutagen 38:329-38. 2001
    ..These S. typhimurium strains may be useful not only for predicting the metabolic activation of promutagens catalyzed by human CYP but also for identifying the CYP form involved...
  90. pmc Uroporphyria produced in mice by iron and 5-aminolaevulinic acid does not occur in Cyp1a2(-/-) null mutant mice
    P R Sinclair
    VA Medical Center, White River Junction, VT 05009, USA
    Biochem J 330:149-53. 1998
    ..These results indicate the absolute requirement for hepatic CYP1A2 in causing experimental uroporphyria under the conditions used...
  91. ncbi Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components
    B Piver
    Laboratory of Biochemistry, EA 948, Faculty of Medicine and I3S, 29285, Cedex, Brest, France
    Toxicol Lett 125:83-91. 2001
    ....
  92. ncbi Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9
    X Wen
    Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland
    Drug Metab Dispos 29:1359-61. 2001
    ..Gemfibrozil may also impair clearance of CYP2C19 and CYP1A2 substrates, but inhibition of other CYP isoforms is unlikely...
  93. ncbi Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples
    J R Baker
    National Research Centre for Environmental Toxicology, Brisbane, Australia
    Biochem Pharmacol 62:713-21. 2001
    ....
  94. ncbi Rat cytochrome p450 1A and 3A enzymes involved in bioactivation of tegafur to 5-fluorouracil and autoinduced by tegafur in liver microsomes
    H Yamazaki
    Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan
    Drug Metab Dispos 29:794-7. 2001
    ..Coadministration of tegafur and P450-inducing drugs could markedly enhance the biotransformation of tegafur into 5-FU via P450 induction...
  95. ncbi Comparative xenobiotic metabolism between Tg.AC and p53+/- genetically altered mice and their respective wild types
    J M Sanders
    Laboratory of Pharmacology and Chemistry, National Toxicology Program, National Institute of Environmental Health Sciences, MD C3 02, P O Box 12233, Research Triangle Park, North Carolina 27709 2233, USA
    Toxicol Sci 61:54-61. 2001
    ....
  96. ncbi Induction and suppression of cytochrome P450 1A by 3,3',4,4',5-pentachlorobiphenyl and its relationship to oxidative stress in the marine fish scup (Stenotomus chrysops)
    J J Schlezinger
    Biology Department, Woods Hole Oceanographic Institution, Redfield 342, MS 32, Woods Hole, MA 02543, USA
    Aquat Toxicol 52:101-15. 2001
    ..However, there appears to be a complex balance between the effects of PeCB on the levels of active CYP1A, ROS release and oxidative stress...
  97. pmc Effect of chronic disulfiram administration on the activities of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and N-acetyltransferase in healthy human subjects
    Reginald F Frye
    Department of Pharmaceutical Sciences, School of Pharmacy, 807 Salk Hall, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Br J Clin Pharmacol 53:155-62. 2002
    ..The purpose of this study was to evaluate the effects of disulfiram given for 11 days on selected drug metabolizing enzyme activities...
  98. ncbi St. John's wort extract induces CYP3A and CYP2E1 in the Swiss Webster mouse
    B J Bray
    Department of Pharmacology and Toxicology, Adams Building Room 238, Great King St, University of Otago Medical School, Dunedin, New Zealand
    Toxicol Sci 66:27-33. 2002
    ....
  99. ncbi Aryl hydrocarbon (Ah) receptor-independent induction of Cyp1a2 gene expression by acenaphthylene and related compounds in B6C3F1 mice
    K Chaloupka
    Texas A and M University, College Station 77843 4466
    Carcinogenesis 15:2835-40. 1994
    ....
  100. ncbi Ursodeoxycholic acid (UDCA) prevents DCA effects on male mouse liver via up-regulation of CYP [correction of CXP] and preservation of BSEP activities
    Moreno Paolini
    Department of Pharmacology, University of Bologna, Bologna, Italy
    Hepatology 36:305-14. 2002
    ..These findings may shed further light on the mechanisms responsible for UDCA's protective role in the treatment of cholestatic liver disease...
  101. ncbi Effect of 3,3',4,4'-tetrachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl on the induction of hepatic lipid peroxidation and cytochrome P-450 associated enzyme activities in rats
    Zaineb Fadhel
    College of Pharmacy, University of Petra, Amman, Jordan
    Toxicology 175:15-25. 2002
    ..The results also indicate a larger time difference between cytochrome P-450 induction and lipid peroxidation for PCB-77. Thus, both PCB-77 and PCB-153 are toxic to cells, but may act via different mechanisms to induce their effects...

Research Grants62

  1. CYP1A1 GENE AND ENVIRONMENTAL TOXICITY
    Daniel Nebert; Fiscal Year: 2005
    ..abstract_text> ..
  2. Interplay between metabolism and FXR activation in scoparone signaling
    Bingfang Yan; Fiscal Year: 2013
    ..Interestingly, scoparone has been found to exert these very activities. Thus, a confirmation on the functional connection between FXR and scoparone will have broad mechanistic and therapeutic implications. ..
  3. Genetic Susceptibility to PCB-induced Motor Dysfunction
    CHRISTINE PERDAN CURRAN; Fiscal Year: 2012
    ..The proposed research is designed to identify neural pathways affected by PCB exposure and humans at highest risk of PCB developmental neurotoxicity using a mouse model that mirrors known genetic variations in humans. ..
  4. ACTIVITY OF P450/1A2 AND 3A4 AND BREAST CANCER RISK
    Wei Zheng; Fiscal Year: 1999
    ..The enzyme activity data collected from this study will be analyzed jointly with data collected from the main study to evaluate the association of CYP1A2 and CYP3A4 activities with breast cancer risk. ..
  5. Glutathione in Environmental Toxicity and Disease
    HOWARD SHERTZER; Fiscal Year: 2007
    ..Our proposed research should therefore help focus future genotype-phenotype association studies between the appropriate DNA variant sites in the GCLC and GCLM genes and disease. ..
  6. RECEPTOR MEDIATED OXIDATIVE STRESS
    HOWARD SHERTZER; Fiscal Year: 2003
    ..These studies will improve our understanding of how PHAHs such as TCDD generate oxidative stress and mutagenesis, leading to better models for risk assessment and novel strategies for intervention in PHAH-mediated toxicity. ..
  7. MECHANISM OF PORPHYRIA CAUSED BY TCDD
    Peter Sinclair; Fiscal Year: 2002
    ..II. To determine whether human CYP1A2 has an essential role in UROgen oxidation and the development of uroporphyria. III. To study the interaction of Fe and CYP1A2 in the development of uroporphyria. ..
  8. ETHANOL EFFECTS ON BONE FORMATION IN PREGNANCY
    Martin Ronis; Fiscal Year: 2006
    ..The role of CYP2E1 and free radicals in the skeletal toxicity of ethanol during these periods will also be studied. ..
  9. PAHs: Balance of Detoxication vs Metabolic Activation
    Daniel Nebert; Fiscal Year: 2009
    ..dissemination of ingested BaP and will be informative in clinical studies in which we would determine which haplotypes of these three human genes might be associated with resistance vs. sensitivity to PAH-induced toxicity and cancer. ..
  10. Molecular Genetics of Cadmium Toxicity
    Daniel W Nebert; Fiscal Year: 2010
    ....
  11. Urinary proteomics in aminoglycoside treated newborns
    Mary Kennedy; Fiscal Year: 2008
    ..The results of this research may allow us to identify infants who are at risk for developing significant injury before it occurs. [unreadable] [unreadable] [unreadable]..
  12. ETHANOL METABOLISM IN PREGNANCY--ROLE OF DIET
    Martin Ronis; Fiscal Year: 2005
    ....
  13. Sphingolipid signaling in olfactory mucosa
    Mary Beth Genter; Fiscal Year: 2004
    ..abstract_text> ..
  14. Extracellular matrix in chloracetanilide carcinogenesis
    Mary Beth Genter; Fiscal Year: 2004
    ..abstract_text> ..
  15. MECHANISM OF INDUCTION OF OLFACTORY TUMORS BY ALACHLOR
    Mary Beth Genter; Fiscal Year: 2002
    ....
  16. GENOTOXICITY IN CYP1A2 DEFICIENT TRANSGENIC MICE
    Daniel Nebert; Fiscal Year: 2002
    ..S. population. ..
  17. High Throughput Liver Toxicity Screening
    James Kelly; Fiscal Year: 2002
    ..The market for such a human toxicity system exceeds $25 million annually. ..
  18. Physiological Importance of Growth Hormone Pulsatility
    Craig Jaffe; Fiscal Year: 2008
    ..The results of this study will add to our understanding of the physiology and pathophysiology of GH action and will help in designing more effective means of GH replacement therapy. [unreadable] [unreadable]..
  19. Dietary Factors in the Etiology of Colorectal Cancer
    Jian Min Yuan; Fiscal Year: 2008
    ..The potential modifying effects of HAA activating genes and tea polyphenols on the HAA-colorectal cancer association will be explored. [unreadable] [unreadable]..
  20. Cytochrome P450 regulation by hyperoxia and nitric oxide
    Xanthi Couroucli; Fiscal Year: 2006
    ..The studies will also help identify appropriate supportive therapies to minimize any adverse effects arising out of this clinically important therapy. ..
  21. Ethnic/Racial Minorities in the Colon CFR
    Loic Le Marchand; Fiscal Year: 2008
    ..abstract_text> ..
  22. Novel approach to measure DNA adducts in humans
    ROBERT TURESKY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  23. Ontogeny of Drug Bioactivation and Idiosyncratic ADRs
    JAMES LEEDER; Fiscal Year: 2007
    ..abstract_text> ..
  24. Effect of Diet on Drug Metabolism in Infants
    Michael Blake; Fiscal Year: 2003
    ..abstract_text> ..
  25. Serum IGFs--Effects of a Soy Intervention in Humans
    Johanna Lampe; Fiscal Year: 2002
    ..It provides an ideal design to evaluate the effects of isoflavones on the IGF system and to explore relationships between IGFs and colonic epithelial cell proliferation in humans. ..
  26. Enhance and Expand University Research Infrastructure
    Carolyn Howard; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  27. Mechanisms of Atypical Drug Kinetics and Interactions
    TIMOTHY TRACY; Fiscal Year: 2008
    ..From these data, computer models will be developed to predict the occurrence of atypical kinetics and potential drug interactions to assist in the drug development process. ..
  28. Molecular Epidemiology of Pancreatic Cancer
    Donghui Li; Fiscal Year: 2008
    ..Such information will be valuable for the primary prevention of this deadly disease. ..
  29. UGT Polymorphisms and Hormonally-Mediated Biomarkers in Premenopausal Women
    Johanna Lampe; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  30. Case-Control Study of Adenoma in Sao Paulo Japanese
    Loic Le Marchand; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  31. Breast Cancer, Benign Breast Disease, and Isoflavone Metabolism in Chinese Women
    Johanna Lampe; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  32. DIET AND DURATION OF CERVICAL HPV INFECTION
    MARC GOODMAN; Fiscal Year: 2009
    ....
  33. Hawaii Colorectal Cancer Family Registry
    Loic Le Marchand; Fiscal Year: 2008
    ..We will also propose a CFR pilot study exploring the feasibility of assessing assorted mating as evidence for population stratification. ..
  34. HOST GENES AND COLONIC BACTERIA--PROBING FOR INHERITANCE
    Johanna Lampe; Fiscal Year: 2002
    ..If we can establish that the equol-producer phenotype is an inherited trait, we can then work to identify the associated genotype and determine more effectively whether this is a biomarker of breast cancer risk. ..
  35. Human Gut Microflora Profiling for Population Studies
    Johanna Lampe; Fiscal Year: 2006
    ..abstract_text> ..
  36. Hypertension Pharmacogenetics
    Julie Johnson; Fiscal Year: 2006
    ..The proposed studies should add substantial new information about antihypertensive pharmacogenetics, and could influence how antihypertensive medications are prescribed in the future. ..
  37. Diet, Genetic Susceptibility and Colorectal Neoplasia
    Loic Le Marchand; Fiscal Year: 2006
    ..Genotyping for random markers will permit to exclude residual confounding by ethnicity. ..
  38. PATHOGENESIS OF ANTICONVULSANT HYPERSENSITIVITY SYNDROME
    JAMES LEEDER; Fiscal Year: 2003
    ..It is anticipated that the basic experimental paradigm employed for these studies can also be applied to other idiosyncratic toxicities with suspected drug bioactivation and immune etiologies. ..
  39. Effects of Arsenic on Cytochromes P450
    RALPH NICHOLS; Fiscal Year: 2005
    ..3) To investigate, in primary cultures of human and rat hepatocytes, the effect of arsenite on translation of the mRNAs of CYPs 1A1, 3A4 and 3A23. ..
  40. BETA-ADRENERGIC RECEPTOR POLYMORPHISMS AND HYPERTENSION
    Julie Johnson; Fiscal Year: 2003
    ..the BAR genotype significantly impacts the BP response to B-blockers could lead to improved patient outcomes, as patients could be genotyped prior to institution of B-blocker therapy, thus avoiding this therapy in those likely to respond ..
  41. GENES, DIET AND CARCINOGEN ACTIVATION IN SMOKERS
    Loic Le Marchand; Fiscal Year: 2004
    ..The elucidation of the main enzymes responsible for carcinogen activation and of the impact of dietary factors on these enzymes would have important implications for cancer prevention. ..
  42. Quantifying the impact of diet on carcinogen exposure
    JAMES FELTON; Fiscal Year: 2003
    ..Once the impact of dietary factors is understood, then it will be possible to emphasize prevention strategies that will eliminate or modify the risk. ..
  43. Pharmacotherapy for Minor Depression
    Robert Howland; Fiscal Year: 2004
    ..The results of this study will have profound public health implications by improving our understanding of the efficacy of SJW and standard antidepressants for the treatment of MinorD. ..
  44. Glucuronidation in Humans--Genotypes and Phenotypes
    Johanna Lampe; Fiscal Year: 2004
    ..The randomized cross-over design will allow us to test efficiently for diet effects within individuals, as well as for gene-by-diet and sex-by-diet interactions. ..
  45. Beta-adrenoceptor genetic polymorphisms and obesity
    Julie Johnson; Fiscal Year: 2002
    ..Additionally, genotyping individuals early in age may help to identify those at increased risk of obesity prior to them becoming obese so that they may take appropriate preventive measures. ..
  46. Pharmacogenetic Epidemiology of Birth Defects and Cancer
    Timothy Rebbeck; Fiscal Year: 2004
    ....
  47. DNA Damage: Fruit & Vegetable Effects in a Feeding Trial
    Johanna Lampe; Fiscal Year: 2005
    ..The existing intervention provides an ideal design in which to evaluate the relationships between biotransformation enzyme systems and DNA damage in humans. ..
  48. Metabolism of Carcinogens and Drugs by Human P450s
    F Guengerich; Fiscal Year: 2005
    ..Successful completion of these collective studies should provide better understanding of the ways in which human P450s catalyze oxidation of carcinogens and drugs and the significance of variations in these enzymes. ..
  49. PharmGKB Experimental Biology Workshop 2005
    TIMOTHY TRACY; Fiscal Year: 2005
    ....
  50. Beta-receptors and cardiovascular pharmacogenomics
    Julie Johnson; Fiscal Year: 2006
    ..abstract_text> ..
  51. REGULATION OF MICROSOMAL HEMOPROTEINS
    LINDA QUATTROCHI; Fiscal Year: 2006
    ..We fully expect that refinements in understanding gene structure, gene expression, and disease outcome can be achieved by the proposed research program. ..
  52. Breast and Bone Density: Impact of Colonic Environment
    Johanna Lampe; Fiscal Year: 2006
    ..If equol-producer phenotype can predict differences in cumulative estrogen exposure / metabolism, it may serve as an early marker of breast cancer risk. ..
  53. Hormone Status Postmenopause: Colonic Bacterial Effects
    Johanna Lampe; Fiscal Year: 2003
    ..The results of this study will provide novel data regarding the relationship of the equol-producer phenotype, a marker of colonic nticrofloral environment, to lifetime estrogen exposure. ..
  54. GLUTATHIONE TRANSFERASES IN HUMANS: DIETARY INFLUENCES
    Johanna Lampe; Fiscal Year: 2006
    ..abstract_text> ..
  55. The TGFbeta Pathway, Gene Variants and Colorectal Neopl*
    Loic Le Marchand; Fiscal Year: 2005
    ..abstract_text> ..
  56. P-glycoprotein and Steroid-Resistant Nephrotic Syndrome
    LYNDA WELAGE; Fiscal Year: 2005
    ..abstract_text> ..
  57. Paraxanthine and Reproductive Effects of Caffeine
    Michael Bracken; Fiscal Year: 2004
    ..abstract_text> ..
  58. DIETARY FACTORS IN THE ETIOLOGY OF CANCER IN SHANGHAI
    Jian Min Yuan; Fiscal Year: 2006
    ..In all instances of diet-cancer investigations, relevant genes with potential modifying effects on the respective diet-cancer associations will be included in the investigations. ..
  59. THE SINGAPORE COHORT STUDY OF DIET AND CANCER
    Jian Min Yuan; Fiscal Year: 2009
    ....
  60. Perinatal Risk of Asthma in Infants of Asthmatic Mothers
    Michael Bracken; Fiscal Year: 2007
    ..Identification of pregnancy and neonatal risk factors for infant asthma may offer opportunities for early prevention. ..