Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFM3MMU)

• DOT Name: DNA polymerase epsilon catalytic subunit A (POLE)
• Synonyms: EC 2.7.7.7; 3'-5' exodeoxyribonuclease; EC 3.1.11.-; DNA polymerase II subunit A
• Gene Name: POLE
• Related Disease:
  Brain neoplasm
  Endometrial carcinoma
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
  POLE-related polyposis and colorectal cancer syndrome
  Type-1 diabetes
  Adult glioblastoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal adenoma
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Dementia
  Endometrial cancer
  Endometriosis
  Epithelial ovarian cancer
  Facial dysmorphism-immunodeficiency-livedo-short stature syndrome
  Familial adenomatous polyposis
  Gastric adenocarcinoma
  Gastric cancer
  Glioblastoma multiforme
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Mismatch repair cancer syndrome
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic adenocarcinoma
  Polyposis
  Stomach cancer
  Triple negative breast cancer
  Adenoma
  Carcinoma
  Melanoma
  Pancreatic cancer
  IMAGe syndrome
  Polymerase proofreading-related adenomatous polyposis
  Hereditary neoplastic syndrome
  Metastatic malignant neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Hereditary nonpolyposis colon cancer
  Liver cancer
  Lynch syndrome
  Marinesco-Sjogren syndrome
  Neoplasm
  Polyp of large intestine
• UniProt ID: DPOE1_HUMAN
• PDB ID: 5VBN; 7PFO; 7PLO
• EC Number: 2.7.7.7; 3.1.11.-
• Pfam ID: PF00136 ; PF03104 ; PF08490
• Sequence:
  MSLRSGGRRRADPGADGEASRDDGATSSVSALKRLERSQWTDKMDLRFGFERLKEPGEKT
  GWLINMHPTEILDEDKRLGSAVDYYFIQDDGSRFKVALPYKPYFYIATRKGCEREVSSFL
  SKKFQGKIAKVETVPKEDLDLPNHLVGLKRNYIRLSFHTVEDLVKVRKEISPAVKKNREQ
  DHASDAYTALLSSVLQRGGVITDEEETSKKIADQLDNIVDMREYDVPYHIRLSIDLKIHV
  AHWYNVRYRGNAFPVEITRRDDLVERPDPVVLAFDIETTKLPLKFPDAETDQIMMISYMI
  DGQGYLITNREIVSEDIEDFEFTPKPEYEGPFCVFNEPDEAHLIQRWFEHVQETKPTIMV
  TYNGDFFDWPFVEARAAVHGLSMQQEIGFQKDSQGEYKAPQCIHMDCLRWVKRDSYLPVG
  SHNLKAAAKAKLGYDPVELDPEDMCRMATEQPQTLATYSVSDAVATYYLYMKYVHPFIFA
  LCTIIPMEPDEVLRKGSGTLCEALLMVQAFHANIIFPNKQEQEFNKLTDDGHVLDSETYV
  GGHVEALESGVFRSDIPCRFRMNPAAFDFLLQRVEKTLRHALEEEEKVPVEQVTNFEEVC
  DEIKSKLASLKDVPSRIECPLIYHLDVGAMYPNIILTNRLQPSAMVDEATCAACDFNKPG
  ANCQRKMAWQWRGEFMPASRSEYHRIQHQLESEKFPPLFPEGPARAFHELSREEQAKYEK
  RRLADYCRKAYKKIHITKVEERLTTICQRENSFYVDTVRAFRDRRYEFKGLHKVWKKKLS
  AAVEVGDAAEVKRCKNMEVLYDSLQLAHKCILNSFYGYVMRKGARWYSMEMAGIVCFTGA
  NIITQARELIEQIGRPLELDTDGIWCVLPNSFPENFVFKTTNVKKPKVTISYPGAMLNIM
  VKEGFTNDQYQELAEPSSLTYVTRSENSIFFEVDGPYLAMILPASKEEGKKLKKRYAVFN
  EDGSLAELKGFEVKRRGELQLIKIFQSSVFEAFLKGSTLEEVYGSVAKVADYWLDVLYSK
  AANMPDSELFELISENRSMSRKLEDYGEQKSTSISTAKRLAEFLGDQMVKDAGLSCRYII
  SRKPEGSPVTERAIPLAIFQAEPTVRKHFLRKWLKSSSLQDFDIRAILDWDYYIERLGSA
  IQKIITIPAALQQVKNPVPRVKHPDWLHKKLLEKNDVYKQKKISELFTLEGRRQVTMAEA
  SEDSPRPSAPDMEDFGLVKLPHPAAPVTVKRKRVLWESQEESQDLTPTVPWQEILGQPPA
  LGTSQEEWLVWLRFHKKKWQLQARQRLARRKRQRLESAEGVLRPGAIRDGPATGLGSFLR
  RTARSILDLPWQIVQISETSQAGLFRLWALVGSDLHCIRLSIPRVFYVNQRVAKAEEGAS
  YRKVNRVLPRSNMVYNLYEYSVPEDMYQEHINEINAELSAPDIEGVYETQVPLLFRALVH
  LGCVCVVNKQLVRHLSGWEAETFALEHLEMRSLAQFSYLEPGSIRHIYLYHHAQAHKALF
  GIFIPSQRRASVFVLDTVRSNQMPSLGALYSAEHGLLLEKVGPELLPPPKHTFEVRAETD
  LKTICRAIQRFLLAYKEERRGPTLIAVQSSWELKRLASEIPVLEEFPLVPICVADKINYG
  VLDWQRHGARRMIRHYLNLDTCLSQAFEMSRYFHIPIGNLPEDISTFGSDLFFARHLQRH
  NHLLWLSPTARPDLGGKEADDNCLVMEFDDQATVEINSSGCYSTVCVELDLQNLAVNTIL
  QSHHVNDMEGADSMGISFDVIQQASLEDMITGGQAASAPASYDETALCSNTFRILKSMVV
  GWVKEITQYHNIYADNQVMHFYRWLRSPSSLLHDPALHRTLHNMMKKLFLQLIAEFKRLG
  SSVIYANFNRIILCTKKRRVEDAIAYVEYITSSIHSKETFHSLTISFSRCWEFLLWMDPS
  NYGGIKGKVSSRIHCGLQDSQKAGGAEDEQENEDDEEERDGEEEEEAEESNVEDLLENNW
  NILQFLPQAASCQNYFLMIVSAYIVAVYHCMKDGLRRSAPGSTPVRRRGASQLSQEAEGA
  VGALPGMITFSQDYVANELTQSFFTITQKIQKKVTGSRNSTELSEMFPVLPGSHLLLNNP
  ALEFIKYVCKVLSLDTNITNQVNKLNRDLLRLVDVGEFSEEAQFRDPCRSYVLPEVICRS
  CNFCRDLDLCKDSSFSEDGAVLPQWLCSNCQAPYDSSAIEMTLVEVLQKKLMAFTLQDLV
  CLKCRGVKETSMPVYCSCAGDFALTIHTQVFMEQIGIFRNIAQHYGMSYLLETLEWLLQK
  NPQLGH
• Function: Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication. Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork. Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication. Involved in DNA synthesis during DNA repair. Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation.
• KEGG Pathway:
  D. replication (hsa03030)
  Base excision repair (hsa03410)
  Nucleotide excision repair (hsa03420)
• Reactome Pathway:
  PCNA-Dependent Long Patch Base Excision Repair (R-HSA-5651801)
  Termination of translesion DNA synthesis (R-HSA-5656169)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)
  Gap-filling DNA repair synthesis and ligation in GG-NER (R-HSA-5696397)
  Dual Incision in GG-NER (R-HSA-5696400)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  DNA replication initiation (R-HSA-68952)
  Activation of the pre-replicative complex (R-HSA-68962)
  Recognition of DNA damage by PCNA-containing replication complex (R-HSA-110314)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain neoplasm	DISY3EKS	Definitive	Genetic Variation	[1]
Endometrial carcinoma	DISXR5CY	Definitive	Genetic Variation	[2]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[3]
Pancreatic ductal carcinoma	DIS26F9Q	Definitive	Altered Expression	[3]
POLE-related polyposis and colorectal cancer syndrome	DISBPX9N	Definitive	Autosomal dominant	[4]
Type-1 diabetes	DIS7HLUB	Definitive	Altered Expression	[5]
Adult glioblastoma	DISVP4LU	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[7]
Colon cancer	DISVC52G	Strong	Genetic Variation	[8]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[9]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[10]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Autosomal dominant	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[12]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[7]
Dementia	DISXL1WY	Strong	Genetic Variation	[13]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[2]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[15]
Facial dysmorphism-immunodeficiency-livedo-short stature syndrome	DISRCEYL	Strong	Autosomal recessive	[16]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[17]
Gastric adenocarcinoma	DISWWLTC	Strong	Genetic Variation	[7]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[18]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[19]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[19]
Lung neoplasm	DISVARNB	Strong	Biomarker	[20]
Mismatch repair cancer syndrome	DISIXHJ2	Strong	Genetic Variation	[21]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[15]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[15]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Genetic Variation	[7]
Polyposis	DISZSPOK	Strong	Genetic Variation	[21]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[18]
Triple negative breast cancer	DISAMG6N	Strong	Genetic Variation	[22]
Adenoma	DIS78ZEV	moderate	Genetic Variation	[23]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[24]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[23]
Pancreatic cancer	DISJC981	moderate	Genetic Variation	[25]
IMAGe syndrome	DISOGW88	Supportive	Autosomal dominant	[26]
Polymerase proofreading-related adenomatous polyposis	DISGMJXH	Supportive	Autosomal dominant	[27]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[28]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Biomarker	[29]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Genetic Variation	[30]
Hereditary nonpolyposis colon cancer	DISPA49R	Limited	Genetic Variation	[31]
Liver cancer	DISDE4BI	Limited	Genetic Variation	[30]
Lynch syndrome	DIS3IW5F	Limited	Genetic Variation	[31]
Marinesco-Sjogren syndrome	DISKEU0B	Limited	Genetic Variation	[32]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[2]
Polyp of large intestine	DISRE1MK	Limited	Genetic Variation	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DNA polymerase epsilon catalytic subunit A (POLE).	[33]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[37]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[38]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[39]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[40]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[41]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[42]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[45]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[46]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[47]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of DNA polymerase epsilon catalytic subunit A (POLE).	[48]

References

• [1] Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma.Fam Cancer. 2019 Apr;18(2):173-178. doi: 10.1007/s10689-018-0102-6.
• [2] Clinical outcomes of patients with POLE mutated endometrioid endometrial cancer.Gynecol Oncol. 2020 Jan;156(1):194-202. doi: 10.1016/j.ygyno.2019.10.028. Epub 2019 Nov 19.
• [3] POLE Score: a comprehensive profiling of programmed death 1 ligand 1 expression in pancreatic ductal adenocarcinoma.Oncotarget. 2019 Feb 22;10(16):1572-1588. doi: 10.18632/oncotarget.26705. eCollection 2019 Feb 22.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Upregulation of the long noncoding RNA lncPolE contributes to intervertebral disc degeneration by negatively regulating DNA polymerase epsilon.Am J Transl Res. 2019 May 15;11(5):2843-2854. eCollection 2019.
• [6] Novel POLE pathogenic germline variant in a family with multiple primary tumors results in distinct mutational signatures.Hum Mutat. 2019 Jan;40(1):36-41. doi: 10.1002/humu.23676. Epub 2018 Nov 20.
• [7] Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.Nat Biotechnol. 2016 Feb;34(2):155-63. doi: 10.1038/nbt.3391. Epub 2015 Nov 30.
• [8] Development of an MSI-positive colon tumor with aberrant DNA methylation in a PPAP patient.J Hum Genet. 2019 Aug;64(8):729-740. doi: 10.1038/s10038-019-0611-7. Epub 2019 May 14.
• [9] The somatic POLE P286R mutation defines a unique subclass of colorectal cancer featuring hypermutation, representing a potential genomic biomarker for immunotherapy.Oncotarget. 2016 Oct 18;7(42):68638-68649. doi: 10.18632/oncotarget.11862.
• [10] Low frequency of POLD1 and POLE exonuclease domain variants in patients with multiple colorectal polyps.Mol Genet Genomic Med. 2019 Apr;7(4):e00603. doi: 10.1002/mgg3.603. Epub 2019 Mar 2.
• [11] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [12] Novel candidates in early-onset familial colorectal cancer.Fam Cancer. 2020 Jan;19(1):1-10. doi: 10.1007/s10689-019-00145-5. Epub 2019 Sep 25.
• [13] The association between eating difficulties and biliary sludge in the gallbladder in older adults with advanced dementia, at end of life.PLoS One. 2019 Jul 16;14(7):e0219538. doi: 10.1371/journal.pone.0219538. eCollection 2019.
• [14] Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma.Mutat Res. 2014 Mar;761:49-52. doi: 10.1016/j.mrfmmm.2014.01.003. Epub 2014 Jan 25.
• [15] Whole-exome sequencing of ovarian cancer families uncovers putative predisposition genes.Int J Cancer. 2020 Apr 15;146(8):2147-2155. doi: 10.1002/ijc.32545. Epub 2019 Jul 16.
• [16] Polymerase 1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome"). J Exp Med. 2012 Dec 17;209(13):2323-30. doi: 10.1084/jem.20121303. Epub 2012 Dec 10.
• [17] Contribution of New Adenomatous Polyposis Predisposition Genes in an Unexplained Attenuated Spanish Cohort by Multigene Panel Testing.Sci Rep. 2019 Jul 8;9(1):9814. doi: 10.1038/s41598-019-46403-5.
• [18] Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population.Carcinogenesis. 2013 Jul;34(7):1536-42. doi: 10.1093/carcin/bgt094. Epub 2013 Mar 15.
• [19] Comprehensive analysis of POLE and POLD1 Gene Variations identifies cancer patients potentially benefit from immunotherapy in Chinese population.Sci Rep. 2019 Oct 31;9(1):15767. doi: 10.1038/s41598-019-52414-z.
• [20] Genetic variation in the DNA repair genes is predictive of outcome in lung cancer.Hum Mol Genet. 2007 Oct 1;16(19):2333-40. doi: 10.1093/hmg/ddm190.
• [21] A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency.Fam Cancer. 2017 Jan;16(1):67-71. doi: 10.1007/s10689-016-9925-1.
• [22] Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study.Hum Genomics. 2019 Jan 10;13(1):4. doi: 10.1186/s40246-018-0186-y.
• [23] POLE mutations in families predisposed to cutaneous melanoma.Fam Cancer. 2015 Dec;14(4):621-8. doi: 10.1007/s10689-015-9826-8.
• [24] Dedifferentiated endometrial carcinomas with neuroendocrine features: a clinicopathologic, immunohistochemical, and molecular genetic study.Hum Pathol. 2018 Feb;72:100-106. doi: 10.1016/j.humpath.2017.11.006. Epub 2017 Nov 11.
• [25] POLE gene hotspot mutations in advanced pancreatic cancer.J Cancer Res Clin Oncol. 2018 Nov;144(11):2161-2166. doi: 10.1007/s00432-018-2746-x. Epub 2018 Sep 7.
• [26] DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency. Am J Hum Genet. 2018 Dec 6;103(6):1038-1044. doi: 10.1016/j.ajhg.2018.10.024. Epub 2018 Nov 29.
• [27] Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet. 2013 Feb;45(2):136-44. doi: 10.1038/ng.2503. Epub 2012 Dec 23.
• [28] Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer.Eur J Hum Genet. 2015 Aug;23(8):1080-4. doi: 10.1038/ejhg.2014.242. Epub 2014 Nov 5.
• [29] High frequency of POLE mutations in synchronous endometrial and ovarian carcinoma.Hum Pathol. 2019 Mar;85:92-100. doi: 10.1016/j.humpath.2018.11.001. Epub 2018 Nov 15.
• [30] Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair.Cell. 2016 Jan 28;164(3):538-49. doi: 10.1016/j.cell.2015.12.050. Epub 2016 Jan 21.
• [31] Risk of colorectal cancer for carriers of a germ-line mutation in POLE or POLD1.Genet Med. 2018 Aug;20(8):890-895. doi: 10.1038/gim.2017.185. Epub 2017 Nov 9.
• [32] Role of immune checkpoint inhibitors in the treatment of colorectal cancer: focus on nivolumab.Expert Opin Biol Ther. 2019 Dec;19(12):1247-1263. doi: 10.1080/14712598.2019.1680636. Epub 2019 Oct 23.
• [33] 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.
• [34] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [35] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [36] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [37] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [38] 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.
• [39] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [40] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [41] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [42] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [43] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [44] Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells. Cell Biol Toxicol. 2021 Dec;37(6):891-913. doi: 10.1007/s10565-020-09579-5. Epub 2021 Jan 7.
• [45] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [46] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [47] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [48] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.