Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID	DTD0244 Transporter Info
Gene Name	SLC28A1
Transporter Name	Concentrative nucleoside transporter 1
Gene ID	9154
UniProt ID	O00337

Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)
Chemical Compound
DT Modulation1	Adenosine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	SLC28A1 protein affects the transport of Adenosine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Valproic Acid results in increased methylation of SLC28A1 gene			[5]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Adenosine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Cytarabine inhibits the reaction SLC28A1 protein results in increased transport of Uridine			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Cytidine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Gemcitabine inhibits the reaction SLC28A1 protein results in increased transport of Uridine			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	Lamivudine inhibits the reaction SLC28A1 protein results in increased transport of Uridine			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation6	SLC28A1 protein results in increased transport of Uridine			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation7	SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation8	Sodium affects the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation9	Thymidine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation10	Zidovudine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Benzo(a)pyrene results in increased methylation of SLC28A1 5' UTR			[17]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Benzo(a)pyrene results in increased methylation of SLC28A1 promoter			[17]
Regulation Mechanism				Transcription Factor Info
Azacitidine	4 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC28A1 protein results in increased susceptibility to Azacitidine			[16]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	SLC28A1 protein results in increased uptake of Azacitidine			[16]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	SLC28A1 protein results in increased uptake of Azacitidine which results in decreased expression of DNMT1 protein			[16]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Sodium affects the reaction SLC28A1 protein results in increased uptake of Azacitidine			[16]
Regulation Mechanism				Transcription Factor Info
bisphenol A	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC28A1 gene			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	bisphenol A results in decreased methylation of SLC28A1 gene			[18]
Regulation Mechanism				Transcription Factor Info
butyraldehyde	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	butyraldehyde results in increased expression of SLC28A1 mRNA			[8]
Regulation Mechanism				Transcription Factor Info
CGP 52608	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	CGP 52608 promotes the reaction RORA protein binds to SLC28A1 gene			[19]
Regulation Mechanism				Transcription Factor Info
clothianidin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	clothianidin results in increased expression of SLC28A1 mRNA			[12]
Regulation Mechanism				Transcription Factor Info
Cytarabine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cytarabine inhibits the reaction SLC28A1 protein results in increased transport of Uridine			[20]
Regulation Mechanism				Transcription Factor Info
Cytidine	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cytidine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	SLC28A1 protein results in increased transport of Cytidine			[20]
Regulation Mechanism				Transcription Factor Info
Decitabine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC28A1 protein results in increased susceptibility to Decitabine			[16]
Regulation Mechanism				Transcription Factor Info
Deoxycytidine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC28A1 protein results in increased transport of Deoxycytidine			[20]
Regulation Mechanism				Transcription Factor Info
Fulvestrant	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC28A1 gene			[18]
Regulation Mechanism				Transcription Factor Info
Gemcitabine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Gemcitabine inhibits the reaction SLC28A1 protein results in increased transport of Uridine			[20]
Regulation Mechanism				Transcription Factor Info
Lamivudine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Lamivudine inhibits the reaction SLC28A1 protein results in increased transport of Uridine			[20]
Regulation Mechanism				Transcription Factor Info
N-Nitrosopyrrolidine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	N-Nitrosopyrrolidine results in decreased expression of SLC28A1 mRNA			[13]
Regulation Mechanism				Transcription Factor Info
Okadaic Acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Okadaic Acid results in decreased expression of SLC28A1 mRNA			[21]
Regulation Mechanism				Transcription Factor Info
Sodium	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sodium affects the reaction SLC28A1 protein results in increased uptake of Azacitidine			[16]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Sodium affects the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
sodium arsenite	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	sodium arsenite results in decreased expression of SLC28A1 mRNA			[11]
Regulation Mechanism				Transcription Factor Info
Thymidine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Thymidine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
tris(2-butoxyethyl) phosphate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	tris(2-butoxyethyl) phosphate affects the expression of SLC28A1 mRNA			[24]
Regulation Mechanism				Transcription Factor Info
Zidovudine	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC28A1 protein affects the transport of Zidovudine			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Zidovudine inhibits the reaction SLC28A1 protein results in increased uptake of Uridine			[14]
Regulation Mechanism				Transcription Factor Info
Nanoparticle
perfluoro-n-nonanoic acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	perfluoro-n-nonanoic acid results in decreased expression of SLC28A1 mRNA			[22]
Regulation Mechanism				Transcription Factor Info
Natural Product
Resveratrol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Plant Extracts co-treated with Resveratrol results in decreased expression of SLC28A1 mRNA			[23]
Regulation Mechanism				Transcription Factor Info
Approved Drug
Adenosine	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Adenosine inhibits the transportation of Uridine by SLC28A1			[1]
Affected Drug/Substrate	Uridine	Modulation Type	Inhibition
Cyclosporine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cyclosporine inhibits the expression of SLC28A1			[2]
Rosiglitazone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Rosiglitazone inhibits the expression of SLC28A1			[3]
Urethane	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Urethane inhibits the expression of SLC28A1			[4]
Valproic Acid	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Valproic Acid inhibits the expression of SLC28A1			[5]
Acetaminophen	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Acetaminophen inhibits the expression of SLC28A1			[6]
Uridine	11 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Uridine inhibits the activity of SLC28A1			[1]
Drug in Phase 1 Trial
Sodium arsenite	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sodium arsenite inhibits the expression of SLC28A1			[11]
Discontinued Drug
Tecadenoson	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Tecadenoson inhibits the transportation of Uridine by SLC28A1			[1]
Affected Drug/Substrate	Uridine	Modulation Type	Inhibition
Mycotoxins
Aflatoxin B1	4 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Aflatoxin B1 inhibits the expression of SLC28A1			[9]
DT Modulation2	Aflatoxin B1 affects the expression of SLC28A1 protein			[2]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Aflatoxin B1 results in increased methylation of SLC28A1 exon			[15]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Aflatoxin B1 results in increased methylation of SLC28A1 gene			[9]
Regulation Mechanism				Transcription Factor Info
Acute Toxic Substance
Formaldehyde	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Formaldehyde increases the expression of SLC28A1			[10]
Carcinogen
Benzo(a)pyrene	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Benzo(a)pyrene inhibits the expression of SLC28A1			[13]
Pesticide/Insecticide
Clothianidin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Clothianidin increases the expression of SLC28A1			[12]
Health and Environmental Toxicant
Butyraldehyde	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Butyraldehyde increases the expression of SLC28A1			[8]
Herbicide
Atrazine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Atrazine increases the expression of SLC28A1			[7]

References
1	Transport of A1 adenosine receptor agonist tecadenoson by human and mouse nucleoside transporters: evidence for blood-brain barrier transport by murine equilibrative nucleoside transporter 1 mENT1. Drug Metab Dispos. 2013 Apr;41(4):916-22.
2	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.
3	Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
4	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
5	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
7	Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
8	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.
9	Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
10	Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842.
11	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.
12	Growth and neurite stimulating effects of the neonicotinoid pesticide clothianidin on human neuroblastoma SH-SY5Y cells. Toxicol Appl Pharmacol. 2019 Nov 15;383:114777.
13	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
14	Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am J Physiol. 1997;272(2 Pt 1):C707-14.
15	Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
16	Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation. Mol Cancer Ther. 2009;8(1):225-31.
17	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
18	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
19	Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
20	Differential transport of cytosine-containing nucleosides by recombinant human concentrative nucleoside transporter protein hCNT1. Nucleosides Nucleotides Nucleic Acids. 2000;19(1-2):415-34.
21	A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
22	Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA) increase triglyceride levels and decrease cholesterogenic gene expression in human HepaRG liver cells. Arch Toxicol. 2020 Sep;94(9):3137-3155.
23	One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.
24	Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq. Toxicol In Vitro. 2018;46:178-188.

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Detail Information of Exogenous Modulation

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