Details of Xenobiotics-DME Interaction (XEOTIC)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0053)
DME Name Dihydrothymine dehydrogenase (DPYD), Homo sapiens DME Info
UniProt ID
DPYD_HUMAN
EC Number    EC: 1.3.1.2     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
CH-CH donor oxidoreductase
NAD/NADP acceptor oxidoreductase
EC: 1.3.1.2
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Interactome
Interactions between Xenobiotics and DME (XEOTIC)
      Health or Environmental Toxicant(s)
                  Acute Toxic Substance Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Formaldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01305   XEOTIC Info Gene Form mRNA
                                 Classification Acute Toxic Substance
                                 DME Modulation Formaldehyde inhibits the expression of DME DPYD [1]
                  Carcinogen Click to Show/Hide the Full List of Xenobiotics:        4 Xenobiotics
                              Benzo(a)pyrene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00898   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Benzo(a)pyrene inhibits the expression of DME DPYD [2]
                              Ethyl methanesulfonate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00772   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Ethyl methanesulfonate inhibits the expression of DME DPYD [1]
                              Sodium bichromate Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01024   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen
                                 DME Modulation Sodium bichromate inhibits the expression of DME DPYD [3]
                              Aflatoxin B1 Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00806   XEOTIC Info Gene Form mRNA
                                 Classification Carcinogen-mycotoxin
                                 DME Modulation Aflatoxin B1 inhibits the expression of DME DPYD [4], [5]
                  Health Hazard/Toxicant Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Butyraldehyde Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00999   XEOTIC Info Gene Form mRNA
                                 Classification Health Hazard
                                 DME Modulation Butyraldehyde inhibits the expression of DME DPYD [6]
      Natural Product(s), Extract(s) or Medicine(s)
                  Natural Mixture Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Tobacco smoke pollution Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00821   XEOTIC Info Gene Form Protein
                                 Classification Natural Mixture
                                 DME Modulation Tobacco smoke pollution inhibits the drug-metabolizing activity of DME DPYD [7]
                  Natural Product Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Heliotrine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01551   XEOTIC Info Gene Form mRNA
                                 Classification Natural Product
                                 DME Modulation Heliotrine inhibits the expression of DME DPYD [8]
                              Pyrrolizidine alkaloid Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO01582   XEOTIC Info Gene Form Protein
                                 Classification Natural Product
                                 DME Modulation Pyrrolizidine alkaloid inhibits the drug-metabolizing activity of DME DPYD [9]
                  Plant Extract Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Plant extracts Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01574   XEOTIC Info Gene Form mRNA
                                 Classification Plant Extract
                                 DME Modulation Plant extracts up-regulates the expression of DME DPYD [10]
                  Traditional Medicine Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Jinfukang Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00760   XEOTIC Info Gene Form mRNA
                                 Classification Traditional Medicine
                                 DME Modulation Jinfukang inhibits the expression of DME DPYD [11]
      Pharmaceutical Agent(s)
                  Approved/Marketed Drug Click to Show/Hide the Full List of Xenobiotics:      13 Xenobiotics
                              Acetaminophen Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00217   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Acetaminophen inhibits the expression of DME DPYD [12]
                              Arsenic trioxide Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00339   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Arsenic trioxide up-regulates the expression of DME DPYD [13]
                              Azathioprine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00007   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Azathioprine inhibits the expression of DME DPYD [14]
                              Capecitabine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00133   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Capecitabine up-regulates the expression of DME DPYD [15]
                              Cisplatin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00334   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cisplatin inhibits the drug-metabolizing activity of DME DPYD [16]
                              Cyclosporine Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00241   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Cyclosporine inhibits the expression of DME DPYD [17], [18]
                              Decitabine Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00168   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Decitabine up-regulates the expression of DME DPYD [19]
                              Docetaxel Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00153   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Docetaxel inhibits the drug-metabolizing activity of DME DPYD [20]
                              Fluorouracil Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00037   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Fluorouracil induces the drug-metabolizing activity of DME DPYD [20], [21]
                              Irinotecan hydrochloride Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00301   XEOTIC Info Gene Form mRNA
                                 Classification Drug Approved by US FDA
                                 DME Modulation Irinotecan hydrochloride inhibits the expression of DME DPYD [22]
                              Paclitaxel Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00256   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Paclitaxel inhibits the drug-metabolizing activity of DME DPYD [23]
                              Temsirolimus Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00229   XEOTIC Info Gene Form Protein
                                 Classification Drug Approved by US FDA
                                 DME Modulation Temsirolimus inhibits the drug-metabolizing activity of DME DPYD [24]
                              Gimeracil Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00472   XEOTIC Info Gene Form Protein
                                 Classification Drug Marketed but not Approved by US FDA
                                 DME Modulation Gimeracil inhibits the drug-metabolizing activity of DME DPYD [25]
                  Drug in Phase 3 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Sulforafan Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01478   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 3
                                 DME Modulation Sulforafan up-regulates the expression of DME DPYD [26]
                  Drug in Phase 2 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Camptothecin Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00597   XEOTIC Info Gene Form Protein
                                 Classification Highest Clinical Status: Phase 2
                                 DME Modulation Camptothecin inhibits the drug-metabolizing activity of DME DPYD [16]
                  Drug in Phase 1 Clinical Trial Click to Show/Hide the Full List of Xenobiotics:        2 Xenobiotics
                              Dinitrochlorobenzene Click to Show/Hide the Detail Inhibition
                                 XEOTIC ID XEO00571   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Dinitrochlorobenzene inhibits the expression of DME DPYD [27]
                              Trichostatin A Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO01492   XEOTIC Info Gene Form mRNA
                                 Classification Highest Clinical Status: Phase 1
                                 DME Modulation Trichostatin A up-regulates the expression of DME DPYD [28], [29]
                  Investigative Agent Click to Show/Hide the Full List of Xenobiotics:        1 Xenobiotics
                              Phenylmercuric acetate Click to Show/Hide the Detail Induction
                                 XEOTIC ID XEO00818   XEOTIC Info Gene Form mRNA
                                 Classification Investigative Agent
                                 DME Modulation Phenylmercuric acetate up-regulates the expression of DME DPYD [30], [31]
References
1 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
2 Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
3 Cellular and molecular effects of prolonged low-level sodium arsenite exposure on human hepatic HepaRG cells. Toxicol Sci. 2018 Apr 1;162(2):676-687.
4 Aflatoxins upregulate CYP3A4 mRNA expression in a process that involves the PXR transcription factor. Toxicol Lett. 2011 Aug 28;205(2):146-53.
5 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
6 Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity. Toxicology. 2015 Aug 6;334:111-21.
7 Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base. J Biochem Mol Toxicol. 2017 Sep;31(9).
8 Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis. Toxicol In Vitro. 2015 Oct;29(7):1669-82.
9 Effects of beta-estradiol and propofol on the 4-methylumbelliferone glucuronidation in recombinant human UGT isozymes 1A1, 1A8 and 1A9. Biopharm Drug Dispos. 2004 Nov;25(8):339-44.
10 PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages. FEBS Lett. 2002 Jun 5;520(1-3):177-81.
11 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
12 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
13 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
14 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
15 DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. Int J Oncol. 2007 Aug;31(2):413-8.
16 Influence of chemotherapeutic agents and cytokines on the expression of 5-fluorouracil-associated enzymes in human colon cancer cell lines. J Gastroenterol. 2006 Feb;41(2):140-50.
17 Cyclosporine A treated in vitro models induce cholestasis response through comparison of phenotype-directed gene expression analysis of in vivo Cyclosporine A-induced cholestasis. Toxicol Lett. 2013 Aug 29;221(3):225-36.
18 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
19 Suppression of DPYD expression in RKO cells via DNA methylation in the regulatory region of the DPYD promoter: a potentially important epigenetic mechanism regulating DPYD expression. Biochem Cell Biol. 2007 Jun;85(3):337-46.
20 Synergistic effects of docetaxel and S-1 by modulating the expression of metabolic enzymes of 5-fluorouracil in human gastric cancer cell lines. Int J Cancer. 2006 Aug 15;119(4):783-91.
21 Expression of dihydropyrimidine dehydrogenase, thymidylate synthase, p53 and p21 in metastatic liver tumor from colorectal cancer after 5-fluorouracil-based chemotherapy. Anticancer Res. 2005 Mar-Apr;25(2B):1237-42.
22 In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
23 Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
24 Pyridoxal oxime derivative potency to reactivate cholinesterases inhibited by organophosphorus compounds. Toxicol Lett. 2016 Nov 16;262:114-122.
25 Alteration of dihydropyrimidine dehydrogenase expression by IFN-alpha affects the antiproliferative effects of 5-fluorouracil in human hepatocellular carcinoma cells. Mol Cancer Ther. 2007 Aug;6(8):2310-8.
26 ACTH regulates steroidogenic gene expression and cortisol biosynthesis in the human adrenal cortex via sphingolipid metabolism. Endocr Res. 2004 Nov;30(4):787-94.
27 Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
28 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
29 Glutathione depletion in antioxidant defense of differentiated NT2-LHON cybrids. Neurobiol Dis. 2007 Mar;25(3):536-44.
30 Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Mol Pharmacol. 2006 Jul;70(1):329-39.
31 Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):86-96.

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