Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT378CU9)

• DOT Name: Dihydrolipoyl dehydrogenase, mitochondrial (DLD)
• Synonyms: EC 1.8.1.4; Dihydrolipoamide dehydrogenase; Glycine cleavage system L protein
• Gene Name: DLD
• Related Disease:
  Colonic neoplasm
  Colorectal adenocarcinoma
  Leigh syndrome
  Maple syrup urine disease
  Methemoglobinemia due to deficiency of methemoglobin reductase
  Prostate cancer
  Prostate carcinoma
  Pyruvate dehydrogenase E3 deficiency
  Schizophrenia
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Cerebellar ataxia
  Colorectal carcinoma
  Congestive heart failure
  Fibrosarcoma
  Friedreich's ataxia
  Gastric cancer
  Glioblastoma multiforme
  leukaemia
  Leukemia
  Leukocyte adhesion deficiency
  Leukocyte adhesion deficiency type II
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Methemoglobinemia
  Multiple sclerosis
  Neuroblastoma
  Non-insulin dependent diabetes
  Stomach cancer
  Type-1/2 diabetes
  Breast carcinoma
  Colon adenocarcinoma
  Pancreatic cancer
  Plasma cell myeloma
  Renal cell carcinoma
  Autism
  Coronary heart disease
  Familial adenomatous polyposis
  Intellectual disability
  Lactic acidosis
  Parkinson disease
  Stroke
• UniProt ID: DLDH_HUMAN
• PDB ID: 1ZMC; 1ZMD; 1ZY8; 2F5Z; 3RNM; 5J5Z; 5NHG; 6HG8; 6I4P; 6I4Q; 6I4R; 6I4S; 6I4T; 6I4U; 6I4Z; 7PSC; 7ZYT
• EC Number: 1.8.1.4
• Pfam ID: PF07992 ; PF02852
• Sequence:
  MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKA
  AQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNL
  DKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNIL
  IATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVT
  AVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGK
  AEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGP
  MLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGK
  FPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDI
  ARVCHAHPTLSEAFREANLAASFGKSINF
• Function: Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion. A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A. In monomeric form may have additional moonlighting function as serine protease. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Citrate cycle (TCA cycle) (hsa00020)
  Glycine, serine and threonine metabolism (hsa00260)
  Valine, leucine and isoleucine degradation (hsa00280)
  Lysine degradation (hsa00310)
  Tryptophan metabolism (hsa00380)
  Pyruvate metabolism (hsa00620)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Propanoate metabolism (hsa00640)
  Lipoic acid metabolism (hsa00785)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  2-Oxocarboxylic acid metabolism (hsa01210)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway:
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)
  Signaling by Retinoic Acid (R-HSA-5362517)
  Glycine degradation (R-HSA-6783984)
  Pyruvate metabolism (R-HSA-70268)
  Branched-chain amino acid catabolism (R-HSA-70895)
  Lysine catabolism (R-HSA-71064)
  Citric acid cycle (TCA cycle) (R-HSA-71403)
  Regulation of pyruvate dehydrogenase (PDH) complex (R-HSA-204174)
• BioCyc Pathway: MetaCyc:HS01727-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colonic neoplasm	DISSZ04P	Definitive	Biomarker	[1]
Colorectal adenocarcinoma	DISPQOUB	Definitive	Biomarker	[2]
Leigh syndrome	DISWQU45	Definitive	Autosomal recessive	[3]
Maple syrup urine disease	DIS61XRH	Definitive	Autosomal recessive	[4]
Methemoglobinemia due to deficiency of methemoglobin reductase	DISZAEZH	Definitive	Genetic Variation	[5]
Prostate cancer	DISF190Y	Definitive	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[6]
Pyruvate dehydrogenase E3 deficiency	DISE8B3S	Definitive	Autosomal recessive	[3]
Schizophrenia	DISSRV2N	Definitive	Biomarker	[7]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[8]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[9]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[10]
Alzheimer disease	DISF8S70	Strong	Biomarker	[11]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[12]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[12]
Breast cancer	DIS7DPX1	Strong	Biomarker	[13]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[15]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[16]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[17]
Friedreich's ataxia	DIS5DV35	Strong	Altered Expression	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[18]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[9]
leukaemia	DISS7D1V	Strong	Biomarker	[19]
Leukemia	DISNAKFL	Strong	Biomarker	[19]
Leukocyte adhesion deficiency	DISEJ9VG	Strong	Genetic Variation	[20]
Leukocyte adhesion deficiency type II	DISYHBB7	Strong	Genetic Variation	[21]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[22]
Lung cancer	DISCM4YA	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[23]
Methemoglobinemia	DISEWENH	Strong	Biomarker	[24]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[25]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[26]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[27]
Stomach cancer	DISKIJSX	Strong	Biomarker	[18]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[16]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[13]
Colon adenocarcinoma	DISDRE0J	moderate	Biomarker	[28]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[29]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[30]
Renal cell carcinoma	DISQZ2X8	moderate	Genetic Variation	[31]
Autism	DISV4V1Z	Limited	Biomarker	[32]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[33]
Familial adenomatous polyposis	DISW53RE	Limited	Genetic Variation	[34]
Intellectual disability	DISMBNXP	Limited	Biomarker	[32]
Lactic acidosis	DISZI1ZK	Limited	Biomarker	[35]
Parkinson disease	DISQVHKL	Limited	Biomarker	[36]
Stroke	DISX6UHX	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[43]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[45]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[50]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[51]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[52]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dihydrolipoyl dehydrogenase, mitochondrial (DLD).	[47]

References

• [1] Soy isoflavones modulate azoxymethane-induced rat colon carcinogenesis exposed pre- and postnatally and inhibit growth of DLD-1 human colon adenocarcinoma cells by increasing the expression of estrogen receptor-beta.J Nutr. 2009 Mar;139(3):474-81. doi: 10.3945/jn.108.099200. Epub 2009 Jan 13.
• [2] A Combination of -Tocotrienol and Ferulic Acid Synergistically Inhibits Telomerase Activity in DLD-1 Human Colorectal Adenocarcinoma Cells.J Nutr Sci Vitaminol (Tokyo). 2016;62(5):281-287. doi: 10.3177/jnsv.62.281.
• [3] 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.
• [4] Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. Hum Mol Genet. 1996 Dec;5(12):1925-30. doi: 10.1093/hmg/5.12.1925.
• [5] Human dihydrolipoamide dehydrogenase (E3) deficiency: Novel insights into the structural basis and molecular pathomechanism.Neurochem Int. 2018 Jul;117:5-14. doi: 10.1016/j.neuint.2017.05.018. Epub 2017 Jun 2.
• [6] Identifying cancer origin using circulating tumor cells.Cancer Biol Ther. 2016 Apr 2;17(4):430-8. doi: 10.1080/15384047.2016.1141839.
• [7] Mutations of the glycine cleavage system genes possibly affect the negative symptoms of schizophrenia through metabolomic profile changes.Psychiatry Clin Neurosci. 2018 Mar;72(3):168-179. doi: 10.1111/pcn.12628. Epub 2018 Jan 31.
• [8] Crumbs3 is a critical factor that regulates invasion and metastasis of colon adenocarcinoma via the specific interaction with FGFR1.Int J Cancer. 2019 Nov 15;145(10):2740-2753. doi: 10.1002/ijc.32336. Epub 2019 Apr 29.
• [9] DR4-Ser424 O-GlcNAcylation Promotes Sensitization of TRAIL-Tolerant Persisters and TRAIL-Resistant Cancer Cells to Death.Cancer Res. 2019 Jun 1;79(11):2839-2852. doi: 10.1158/0008-5472.CAN-18-1991. Epub 2019 Apr 15.
• [10] Minimization of energy transduction confers resistance to phosphine in the rice weevil, Sitophilus oryzae.Sci Rep. 2019 Oct 10;9(1):14605. doi: 10.1038/s41598-019-50972-w.
• [11] 5-Methoxyindole-2-carboxylic acid (MICA) suppresses A-mediated pathology in C. elegans.Exp Gerontol. 2018 Jul 15;108:215-225. doi: 10.1016/j.exger.2018.04.021. Epub 2018 Apr 27.
• [12] Low Cytochrome Oxidase 1 Links Mitochondrial Dysfunction to Atherosclerosis in Mice and Pigs.PLoS One. 2017 Jan 25;12(1):e0170307. doi: 10.1371/journal.pone.0170307. eCollection 2017.
• [13] Heart toxicity from breast cancer radiotherapy : Current findings, assessment, and prevention.Strahlenther Onkol. 2019 Jan;195(1):1-12. doi: 10.1007/s00066-018-1378-z. Epub 2018 Oct 11.
• [14] Lipoamide dehydrogenase: rapid heat inactivation in platelets of patients with recessively inherited ataxia.Neurology. 1981 Feb;31(2):199-202. doi: 10.1212/wnl.31.2.199.
• [15] Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells.Mol Med Rep. 2019 Apr;19(4):2767-2773. doi: 10.3892/mmr.2019.9940. Epub 2019 Feb 5.
• [16] Cardiac Biomarkers Predict Large Vessel Occlusion in Patients with Ischemic Stroke.J Stroke Cerebrovasc Dis. 2019 Jun;28(6):1726-1731. doi: 10.1016/j.jstrokecerebrovasdis.2019.02.013. Epub 2019 Mar 19.
• [17] Oncogenes and Angiogenesis: down-regulation of thrombospondin-1 in normal fibroblasts exposed to factors from cancer cells harboring mutant ras.Cancer Res. 2005 Oct 1;65(19):8878-86. doi: 10.1158/0008-5472.CAN-05-1479.
• [18] Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines.Cancer Chemother Pharmacol. 2012 Jun;69(6):1601-15. doi: 10.1007/s00280-012-1869-z. Epub 2012 Apr 29.
• [19] Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIalpha subunit of protein kinase A after oral administration. Proc Natl Acad Sci U S A. 1999 Nov23;96(24):13989-94.
• [20] A new mutation in the KINDLIN-3 gene ablates integrin-dependent leukocyte, platelet, and osteoclast function in a patient with leukocyte adhesion deficiency-III.Pediatr Blood Cancer. 2015 Sep;62(9):1677-9. doi: 10.1002/pbc.25537. Epub 2015 Apr 8.
• [21] Congenital disorders involving defective N-glycosylation of proteins.Cell Mol Life Sci. 2001 Jul;58(8):1085-104. doi: 10.1007/PL00000923.
• [22] Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression.Mol Cancer. 2017 Jan 21;16(1):17. doi: 10.1186/s12943-017-0581-3.
• [23] Genetic determinants of methotrexate responsiveness and resistance in colon cancer cells.Oncogene. 2005 Oct 13;24(45):6842-7. doi: 10.1038/sj.onc.1208834.
• [24] NADH-diaphorase deficiency identified in a patient with congenital methaemoglobinaemia detected by pulse oximetry.Intensive Care Med. 1998 Jul;24(7):706-8. doi: 10.1007/s001340050648.
• [25] Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions.J Neuropathol Exp Neurol. 1997 Jan;56(1):10-20. doi: 10.1097/00005072-199701000-00002.
• [26] Targeting c-kit receptor in neuroblastomas and colorectal cancers using stem cell factor (SCF)-based recombinant bacterial toxins.Appl Microbiol Biotechnol. 2016 Jan;100(1):263-77. doi: 10.1007/s00253-015-6978-2. Epub 2015 Oct 1.
• [27] Chronic Inhibition of Mitochondrial Dihydrolipoamide Dehydrogenase (DLDH) as an Approach to Managing Diabetic Oxidative Stress.Antioxidants (Basel). 2019 Feb 2;8(2):32. doi: 10.3390/antiox8020032.
• [28] Simultaneous use of erythropoietin and LFM-A13 as a new therapeutic approach for colorectal cancer.Br J Pharmacol. 2018 Mar;175(5):743-762. doi: 10.1111/bph.14099. Epub 2018 Jan 25.
• [29] New 1-phthalazinone Scaffold based Compounds: Design, Synthesis, Cytotoxicity and Protein Kinase Inhibition Activity.Mini Rev Med Chem. 2018;18(20):1759-1774. doi: 10.2174/1389557518666180903153254.
• [30] Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity.ChemMedChem. 2018 Sep 19;13(18):1895-1908. doi: 10.1002/cmdc.201800320. Epub 2018 Aug 5.
• [31] Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin: expression and effects on proliferation.Clin Sci (Lond). 2002 Aug;103 Suppl 48:35S-38S. doi: 10.1042/CS103S035S.
• [32] Neuropsychological functioning of siblings of children with autism, siblings of children with developmental language delay, and siblings of children with mental retardation of unknown genetic etiology.J Autism Dev Disord. 2007 Mar;37(3):537-52. doi: 10.1007/s10803-006-0185-z.
• [33] Hybrid coronary revascularization versus off-pump coronary artery bypass grafting and percutaneous coronary intervention for the treatment of two-vessel coronary artery disease with proximal left anterior descending artery stenosis.J Thorac Dis. 2019 Jun;11(6):2402-2409. doi: 10.21037/jtd.2019.05.54.
• [34] The Discovery and Characterization of K-756, a Novel Wnt/-Catenin Pathway Inhibitor Targeting Tankyrase.Mol Cancer Ther. 2016 Jul;15(7):1525-34. doi: 10.1158/1535-7163.MCT-15-0938. Epub 2016 Apr 25.
• [35] Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.Pediatr Neurol. 1996 Jan;14(1):69-71. doi: 10.1016/0887-8994(96)00005-7.
• [36] CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients.Neurobiol Aging. 2017 Nov;59:1-9. doi: 10.1016/j.neurobiolaging.2017.06.028. Epub 2017 Jul 11.
• [37] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [38] 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.
• [39] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [40] 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.
• [41] 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.
• [42] 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.
• [43] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [44] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [45] Resveratrol-induced cell growth inhibition and apoptosis is associated with modulation of phosphoglycerate mutase B in human prostate cancer cells: two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry evaluation. Cancer Detect Prev. 2004;28(6):443-52. doi: 10.1016/j.cdp.2004.08.009.
• [46] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [47] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [48] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [49] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [50] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [51] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [52] Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses. Toxicology. 2023 Jan 15;484:153413. doi: 10.1016/j.tox.2022.153413. Epub 2022 Dec 26.