Details of Drug Off-Target (DOT)

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

• DOT Name: Chromodomain-helicase-DNA-binding protein 7 (CHD7)
• Synonyms: CHD-7; EC 3.6.4.12; ATP-dependent helicase CHD7
• Gene Name: CHD7
• Related Disease:
  CHARGE syndrome
  Adult glioblastoma
  Advanced cancer
  Autism spectrum disorder
  Breast carcinoma
  Deafness
  DiGeorge syndrome
  Ear malformation
  Glioblastoma multiforme
  Hypogonadism
  Hypogonadotropic hypogonadism 5 with or without anosmia
  Hypogonadotropic hypogonadism 7 with or without anosmia
  Immunodeficiency
  Intellectual disability
  Isolated cleft palate
  Major depressive disorder
  Microphthalmia
  Myopathy
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Sensorineural hearing loss disorder
  Severe combined immunodeficiency
  Shprintzen-Goldberg syndrome
  Vesicoureteral reflux
  Cryptorchidism
  Movement disorder
  Rheumatoid arthritis
  Hypogonadotropic hypogonadism
  Kallmann syndrome
  Omenn syndrome
  Autism
  Chromosomal disorder
  Cleft lip/palate
  Coloboma
  Congenital hypogonadotropic hypogonadism
  Gastroesophageal reflux disease
  Hypothyroidism
  Klinefelter syndrome
• UniProt ID: CHD7_HUMAN
• PDB ID: 2CKC; 2V0E; 2V0F
• EC Number: 3.6.4.12
• Pfam ID: PF07533 ; PF00385 ; PF00271 ; PF00176
• Sequence:
  MADPGMMSLFGEDGNIFSEGLEGLGECGYPENPVNPMGQQMPIDQGFASLQPSLHHPSTN
  QNQTKLTHFDHYNQYEQQKMHLMDQPNRMMSNTPGNGLASPHSQYHTPPVPQVPHGGSGG
  GQMGVYPGMQNERHGQSFVDSSSMWGPRAVQVPDQIRAPYQQQQPQPQPPQPAPSGPPAQ
  GHPQHMQQMGSYMARGDFSMQQHGQPQQRMSQFSQGQEGLNQGNPFIATSGPGHLSHVPQ
  QSPSMAPSLRHSVQQFHHHPSTALHGESVAHSPRFSPNPPQQGAVRPQTLNFSSRSQTVP
  SPTINNSGQYSRYPYSNLNQGLVNNTGMNQNLGLTNNTPMNQSVPRYPNAVGFPSNSGQG
  LMHQQPIHPSGSLNQMNTQTMHPSQPQGTYASPPPMSPMKAMSNPAGTPPPQVRPGSAGI
  PMEVGSYPNMPHPQPSHQPPGAMGIGQRNMGPRNMQQSRPFIGMSSAPRELTGHMRPNGC
  PGVGLGDPQAIQERLIPGQQHPGQQPSFQQLPTCPPLQPHPGLHHQSSPPHPHHQPWAQL
  HPSPQNTPQKVPVHQHSPSEPFLEKPVPDMTQVSGPNAQLVKSDDYLPSIEQQPQQKKKK
  KKNNHIVAEDPSKGFGKDDFPGGVDNQELNRNSLDGSQEEKKKKKRSKAKKDPKEPKEPK
  EKKEPKEPKTPKAPKIPKEPKEKKAKTATPKPKSSKKSSNKKPDSEASALKKKVNKGKTE
  GSENSDLDKTPPPSPPPEEDEDPGVQKRRSSRQVKRKRYTEDLEFKISDEEADDADAAGR
  DSPSNTSQSEQQESVDAEGPVVEKIMSSRSVKKQKESGEEVEIEEFYVKYKNFSYLHCQW
  ASIEDLEKDKRIQQKIKRFKAKQGQNKFLSEIEDELFNPDYVEVDRIMDFARSTDDRGEP
  VTHYLVKWCSLPYEDSTWERRQDIDQAKIEEFEKLMSREPETERVERPPADDWKKSESSR
  EYKNNNKLREYQLEGVNWLLFNWYNMRNCILADEMGLGKTIQSITFLYEIYLKGIHGPFL
  VIAPLSTIPNWEREFRTWTELNVVVYHGSQASRRTIQLYEMYFKDPQGRVIKGSYKFHAI
  ITTFEMILTDCPELRNIPWRCVVIDEAHRLKNRNCKLLEGLKMMDLEHKVLLTGTPLQNT
  VEELFSLLHFLEPSRFPSETTFMQEFGDLKTEEQVQKLQAILKPMMLRRLKEDVEKNLAP
  KEETIIEVELTNIQKKYYRAILEKNFTFLSKGGGQANVPNLLNTMMELRKCCNHPYLING
  AEEKILEEFKETHNAESPDFQLQAMIQAAGKLVLIDKLLPKLKAGGHRVLIFSQMVRCLD
  ILEDYLIQRRYPYERIDGRVRGNLRQAAIDRFSKPDSDRFVFLLCTRAGGLGINLTAADT
  CIIFDSDWNPQNDLQAQARCHRIGQSKSVKIYRLITRNSYEREMFDKASLKLGLDKAVLQ
  SMSGRENATNGVQQLSKKEIEDLLRKGAYGALMDEEDEGSKFCEEDIDQILLRRTHTITI
  ESEGKGSTFAKASFVASGNRTDISLDDPNFWQKWAKKAELDIDALNGRNNLVIDTPRVRK
  QTRLYSAVKEDELMEFSDLESDSEEKPCAKPRRPQDKSQGYARSECFRVEKNLLVYGWGR
  WTDILSHGRYKRQLTEQDVETICRTILVYCLNHYKGDENIKSFIWDLITPTADGQTRALV
  NHSGLSAPVPRGRKGKKVKAQSTQPVVQDADWLASCNPDALFQEDSYKKHLKHHCNKVLL
  RVRMLYYLRQEVIGDQADKILEGADSSEADVWIPEPFHAEVPADWWDKEADKSLLIGVFK
  HGYEKYNSMRADPALCFLERVGMPDAKAIAAEQRGTDMLADGGDGGEFDREDEDPEYKPT
  RTPFKDEIDEFANSPSEDKEESMEIHATGKHSESNAELGQLYWPNTSTLTTRLRRLITAY
  QRSYKRQQMRQEALMKTDRRRRRPREEVRALEAEREAIISEKRQKWTRREEADFYRVVST
  FGVIFDPVKQQFDWNQFRAFARLDKKSDESLEKYFSCFVAMCRRVCRMPVKPDDEPPDLS
  SIIEPITEERASRTLYRIELLRKIREQVLHHPQLGERLKLCQPSLDLPEWWECGRHDRDL
  LVGAAKHGVSRTDYHILNDPELSFLDAHKNFAQNRGAGNTSSLNPLAVGFVQTPPVISSA
  HIQDERVLEQAEGKVEEPENPAAKEKCEGKEEEEETDGSGKESKQECEAEASSVKNELKG
  VEVGADTGSKSISEKGSEEDEEEKLEDDDKSEESSQPEAGAVSRGKNFDEESNASMSTAR
  DETRDGFYMEDGDPSVAQLLHERTFAFSFWPKDRVMINRLDNICEAVLKGKWPVNRRQMF
  DFQGLIPGYTPTTVDSPLQKRSFAELSMVGQASISGSEDITTSPQLSKEDALNLSVPRQR
  RRRRRKIEIEAERAAKRRNLMEMVAQLRESQVVSENGQEKVVDLSKASREATSSTSNFSS
  LSSKFILPNVSTPVSDAFKTQMELLQAGLSRTPTRHLLNGSLVDGEPPMKRRRGRRKNVE
  GLDLLFMSHKRTSLSAEDAEVTKAFEEDIETPPTRNIPSPGQLDPDTRIPVINLEDGTRL
  VGEDAPKNKDLVEWLKLHPTYTVDMPSYVPKNADVLFSSFQKPKQKRHRCRNPNKLDINT
  LTGEERVPVVNKRNGKKMGGAMAPPMKDLPRWLEENPEFAVAPDWTDIVKQSGFVPESMF
  DRLLTGPVVRGEGASRRGRRPKSEIARAAAAAAAVASTSGINPLLVNSLFAGMDLTSLQN
  LQNLQSLQLAGLMGFPPGLATAATAGGDAKNPAAVLPLMLPGMAGLPNVFGLGGLLNNPL
  SAATGNTTTASSQGEPEDSTSKGEEKGNENEDENKDSEKSTDAVSAADSANGSVGAATAP
  AGLPSNPLAFNPFLLSTMAPGLFYPSMFLPPGLGGLTLPGFPALAGLQNAVGSSEEKAAD
  KAEGGPFKDGETLEGSDAEESLDKTAESSLLEDEIAQGEELDSLDGGDEIENNENDE
• Function: Probable transcription regulator. Maybe involved in the in 45S precursor rRNA production.
• Tissue Specificity: Widely expressed in fetal and adult tissues.

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
CHARGE syndrome	DISKD3CW	Definitive	Autosomal dominant	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Deafness	DISKCLH4	Strong	Biomarker	[6]
DiGeorge syndrome	DIST1RKO	Strong	Genetic Variation	[7]
Ear malformation	DISVJGPS	Strong	Genetic Variation	[8]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Hypogonadism	DISICMNI	Strong	Genetic Variation	[9]
Hypogonadotropic hypogonadism 5 with or without anosmia	DISRB12X	Strong	Autosomal dominant	[10]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Strong	Genetic Variation	[11]
Immunodeficiency	DIS093I0	Strong	Biomarker	[12]
Intellectual disability	DISMBNXP	Strong	Biomarker	[4]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[13]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[14]
Microphthalmia	DISGEBES	Strong	Genetic Variation	[15]
Myopathy	DISOWG27	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[17]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[18]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Genetic Variation	[19]
Shprintzen-Goldberg syndrome	DISQH6P3	Strong	Genetic Variation	[7]
Vesicoureteral reflux	DISUL6SA	Strong	Genetic Variation	[20]
Cryptorchidism	DISYUD2P	moderate	Genetic Variation	[21]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[22]
Rheumatoid arthritis	DISTSB4J	moderate	Altered Expression	[23]
Hypogonadotropic hypogonadism	DIS8JSKR	Supportive	Autosomal dominant	[10]
Kallmann syndrome	DISO3HDG	Supportive	Autosomal dominant	[10]
Omenn syndrome	DIS2C887	Supportive	Autosomal recessive	[24]
Autism	DISV4V1Z	Limited	Genetic Variation	[22]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[25]
Cleft lip/palate	DIS14IG3	Limited	Genetic Variation	[26]
Coloboma	DISP39N5	Limited	Genetic Variation	[27]
Congenital hypogonadotropic hypogonadism	DISEV092	Limited	Genetic Variation	[8]
Gastroesophageal reflux disease	DISQ8G5S	Limited	Genetic Variation	[11]
Hypothyroidism	DISR0H6D	Limited	Genetic Variation	[28]
Klinefelter syndrome	DISOUI7W	Limited	Altered Expression	[29]

5 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 Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[30]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[41]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[33]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[34]
Marinol	DM70IK5	Approved	Marinol increases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[36]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[38]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Chromodomain-helicase-DNA-binding protein 7 (CHD7).	[42]

References

• [1] 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.
• [2] CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature.Sci Rep. 2019 Mar 8;9(1):3952. doi: 10.1038/s41598-019-39564-w.
• [3] miR-30 disrupts senescence and promotes cancer by targeting both p16(INK4A) and DNA damage pathways.Oncogene. 2018 Oct;37(42):5618-5632. doi: 10.1038/s41388-018-0358-1. Epub 2018 Jun 15.
• [4] Regulation of neuronal connectivity in the mammalian brain by chromatin remodeling.Curr Opin Neurobiol. 2019 Dec;59:59-68. doi: 10.1016/j.conb.2019.04.010. Epub 2019 May 28.
• [5] Genotranscriptomic meta-analysis of the CHD family chromatin remodelers in human cancers - initial evidence of an oncogenic role for CHD7.Mol Oncol. 2017 Oct;11(10):1348-1360. doi: 10.1002/1878-0261.12104. Epub 2017 Jul 21.
• [6] An intronic mutation in Chd7 creates a cryptic splice site, causing aberrant splicing in a mouse model of CHARGE syndrome.Sci Rep. 2018 Apr 3;8(1):5482. doi: 10.1038/s41598-018-23856-8.
• [7] Establishment of immunity against Epstein-Barr virus infection in a patient with CHARGE/complete DiGeorge syndrome after peripheral blood lymphocyte transfusion.Pediatr Transplant. 2019 Jun;23(4):e13424. doi: 10.1111/petr.13424. Epub 2019 Apr 29.
• [8] High frequency of CHD7 mutations in congenital hypogonadotropic hypogonadism.Sci Rep. 2019 Feb 7;9(1):1597. doi: 10.1038/s41598-018-38178-y.
• [9] Expanding the CHARGE Geno-Phenotype: A Girl with Novel CHD7 Deletion, Hypogonadotropic Hypogonadism, and Agenesis of Uterus and Ovaries.Horm Res Paediatr. 2016;85(4):288-90. doi: 10.1159/000443308. Epub 2016 Jan 8.
• [10] Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2008 Oct;83(4):511-9. doi: 10.1016/j.ajhg.2008.09.005. Epub 2008 Oct 2.
• [11] Phenotypic Spectrum of Idiopathic Hypogonadotropic Hypogonadism Patients With CHD7 Variants From a Large Chinese Cohort.J Clin Endocrinol Metab. 2020 May 1;105(5):dgz182. doi: 10.1210/clinem/dgz182.
• [12] Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism.Eur J Pediatr. 2010 Jul;169(7):839-44. doi: 10.1007/s00431-009-1126-6. Epub 2010 Jan 6.
• [13] Craniofacial anomalies in twins.Plast Reconstr Surg. 1991 Jan;87(1):16-23. doi: 10.1097/00006534-199101000-00004.
• [14] Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.Neuropsychopharmacology. 2018 Sep;43(10):2146-2153. doi: 10.1038/s41386-018-0078-9. Epub 2018 Apr 27.
• [15] Identification of novel pathogenic variants and novel gene-phenotype correlations in Mexican subjects with microphthalmia and/or anophthalmia by next-generation sequencing.J Hum Genet. 2018 Nov;63(11):1169-1180. doi: 10.1038/s10038-018-0504-1. Epub 2018 Sep 4.
• [16] Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7-related disease.Eur J Hum Genet. 2016 Aug;24(8):1216-9. doi: 10.1038/ejhg.2015.276. Epub 2016 Jan 27.
• [17] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [18] Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.BMC Med Genomics. 2018 Jul 9;11(1):58. doi: 10.1186/s12920-018-0375-5.
• [19] Disseminated BCG pneumonitis revealing severe combined immunodeficiencyxs in CHARGE syndrome.Pediatr Pulmonol. 2017 Feb;52(2):E4-E6. doi: 10.1002/ppul.23533. Epub 2016 Nov 22.
• [20] The CHARGE association and athyreosis.J Med Genet. 1991 Mar;28(3):207-8. doi: 10.1136/jmg.28.3.207.
• [21] Hypogonadism and CHARGE association.Am J Med Genet. 2000 Sep 18;94(3):228-31. doi: 10.1002/1096-8628(20000918)94:3<228::aid-ajmg8>3.0.co;2-h.
• [22] Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria.Am J Med Genet A. 2016 Feb;170A(2):344-354. doi: 10.1002/ajmg.a.37435. Epub 2015 Nov 21.
• [23] CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development.JCI Insight. 2018 Feb 22;3(4):e97440. doi: 10.1172/jci.insight.97440. eCollection 2018 Feb 22.
• [24] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [25] Increased paternal age in CHARGE association.Clin Genet. 1996 Dec;50(6):548-50. doi: 10.1111/j.1399-0004.1996.tb02736.x.
• [26] Molecular genetic and clinical delineation of 22 patients with congenital hypogonadotropic hypogonadism.J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1111-1118. doi: 10.1515/jpem-2017-0035.
• [27] Chromodomain Helicase DNA-Binding Protein 7 Is Suppressed in the Perinecrotic/Ischemic Microenvironment and Is a Novel Regulator of Glioblastoma Angiogenesis.Stem Cells. 2019 Apr;37(4):453-462. doi: 10.1002/stem.2969. Epub 2019 Jan 24.
• [28] Endocrine and radiological studies in patients with molecularly confirmed CHARGE syndrome.J Clin Endocrinol Metab. 2008 Mar;93(3):920-4. doi: 10.1210/jc.2007-1419. Epub 2007 Dec 18.
• [29] Sema3a plays a role in the pathogenesis of CHARGE syndrome.Hum Mol Genet. 2018 Apr 15;27(8):1343-1352. doi: 10.1093/hmg/ddy045.
• [30] 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.
• [31] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [32] 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.
• [33] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [34] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [35] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [36] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [37] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [38] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [39] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [40] 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.
• [41] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [42] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.