Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVM78XM)

• DOT Name: Folliculin (FLCN)
• Synonyms: BHD skin lesion fibrofolliculoma protein; Birt-Hogg-Dube syndrome protein
• Gene Name: FLCN
• Related Disease:
  Obsolete Birt-Hogg-Dube syndrome
  Adenocarcinoma
  Ataxia-telangiectasia
  Breast cancer
  Breast carcinoma
  Clear cell adenocarcinoma
  Colonic neoplasm
  Colorectal neoplasm
  Cystic kidney disease
  Familial spontaneous pneumothorax
  Kidney cancer
  Liver cancer
  Lung neoplasm
  Malignant soft tissue neoplasm
  Osteoporosis
  Papillary renal cell carcinoma
  Potocki-Lupski syndrome
  Pulmonary emphysema
  Renal carcinoma
  Sarcoma
  Smith-Magenis syndrome
  Thyroid gland carcinoma
  Trichohepatoenteric syndrome
  Tuberous sclerosis
  Von hippel-lindau disease
  Carcinoma
  Hereditary neoplastic syndrome
  Advanced cancer
  Amyotrophic lateral sclerosis
  Asthma
  Colorectal cancer
  Connective tissue disorder
  Gastric neoplasm
  Hamartoma
  High blood pressure
  Pneumothorax
  Pulmonary disease
  Thyroid cancer
  Thyroid tumor
• UniProt ID: FLCN_HUMAN
• PDB ID: 3V42; 6NZD; 6ULG; 8DHB
• Pfam ID: PF11704 ; PF16692
• Sequence:
  MNAIVALCHFCELHGPRTLFCTEVLHAPLPQGDGNEDSPGQGEQAEEEEGGIQMNSRMRA
  HSPAEGASVESSSPGPKKSDMCEGCRSLAAGHPGYISHDKETSIKYVSHQHPSHPQLFSI
  VRQACVRSLSCEVCPGREGPIFFGDEQHGFVFSHTFFIKDSLARGFQRWYSIITIMMDRI
  YLINSWPFLLGKVRGIIDELQGKALKVFEAEQFGCPQRAQRMNTAFTPFLHQRNGNAARS
  LTSLTSDDNLWACLHTSFAWLLKACGSRLTEKLLEGAPTEDTLVQMEKLADLEEESESWD
  NSEAEEEEKAPVLPESTEGRELTQGPAESSSLSGCGSWQPRKLPVFKSLRHMRQVLGAPS
  FRMLAWHVLMGNQVIWKSRDVDLVQSAFEVLRTMLPVGCVRIIPYSSQYEEAYRCNFLGL
  SPHVQIPPHVLSSEFAVIVEVHAAARSTLHPVGCEDDQSLSKYEFVVTSGSPVAADRVGP
  TILNKIEAALTNQNLSVDVVDQCLVCLKEEWMNKVKVLFKFTKVDSRPKEDTQKLLSILG
  ASEEDNVKLLKFWMTGLSKTYKSHLMSTVRSPTASESRN
• Function: Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis. GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3. Activates mTORC1 by acting as a GTPase-activating protein: specifically stimulates GTP hydrolysis by RagC/RRAGC or RagD/RRAGD, promoting the conversion to the GDP-bound state of RagC/RRAGC or RagD/RRAGD, and thereby activating the kinase activity of mTORC1. The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients. Acts as a key component for non-canonical mTORC1-dependent control of the MiT/TFE factors TFEB and TFE3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1. In low-amino acid conditions, the lysosomal folliculin complex (LFC) is formed on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, inactivates mTORC1 and maximizes nuclear translocation of TFEB and TFE3. Upon amino acid restimulation, RagA/RRAGA (or RagB/RRAGB) nucleotide exchange promotes disassembly of the LFC complex and liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3. Indirectly acts as a positive regulator of Wnt signaling by promoting mTOR-dependent cytoplasmic retention of MiT/TFE factor TFE3. Required for the exit of hematopoietic stem cell from pluripotency by promoting mTOR-dependent cytoplasmic retention of TFE3, thereby increasing Wnt signaling. Acts as an inhibitor of browning of adipose tissue by regulating mTOR-dependent cytoplasmic retention of TFE3. Involved in the control of embryonic stem cells differentiation; together with LAMTOR1 it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation. In response to flow stress, regulates STK11/LKB1 accumulation and mTORC1 activation through primary cilia: may act by recruiting STK11/LKB1 to primary cilia for activation of AMPK resided at basal bodies, causing mTORC1 down-regulation. Together with FNIP1 and/or FNIP2, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy. Required for starvation-induced perinuclear clustering of lysosomes by promoting association of RILP with its effector RAB34. Regulates glycolysis by binding to lactate dehydrogenase LDHA, acting as an uncompetitive inhibitor.
• Tissue Specificity: Expressed in most tissues tested, including skin, lung, kidney, heart, testis and stomach.
• KEGG Pathway:
  mTOR sig.ling pathway (hsa04150)
  Re.l cell carcinoma (hsa05211)
• Reactome Pathway: Amino acids regulate mTORC1 (R-HSA-9639288)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsolete Birt-Hogg-Dube syndrome	DISL08HF	Definitive	Autosomal dominant	[1]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[4]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[4]
Clear cell adenocarcinoma	DISYUGHZ	Strong	Biomarker	[5]
Colonic neoplasm	DISSZ04P	Strong	Genetic Variation	[6]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[7]
Cystic kidney disease	DISRT1LM	Strong	Genetic Variation	[8]
Familial spontaneous pneumothorax	DISNM7SU	Strong	Autosomal dominant	[9]
Kidney cancer	DISBIPKM	Strong	Genetic Variation	[10]
Liver cancer	DISDE4BI	Strong	Biomarker	[11]
Lung neoplasm	DISVARNB	Strong	Biomarker	[2]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[12]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[13]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[14]
Potocki-Lupski syndrome	DISUOI38	Strong	Biomarker	[15]
Pulmonary emphysema	DIS5M7HZ	Strong	Biomarker	[16]
Renal carcinoma	DISER9XT	Strong	Autosomal dominant	[9]
Sarcoma	DISZDG3U	Strong	Biomarker	[12]
Smith-Magenis syndrome	DISG4G6X	Strong	Genetic Variation	[17]
Thyroid gland carcinoma	DISMNGZ0	Strong	Genetic Variation	[18]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[19]
Tuberous sclerosis	DISEMUGZ	Strong	Biomarker	[20]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Genetic Variation	[21]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[22]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[23]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[24]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[25]
Asthma	DISW9QNS	Limited	Altered Expression	[26]
Colorectal cancer	DISNH7P9	Limited	Autosomal dominant	[27]
Connective tissue disorder	DISKXBS3	Limited	Biomarker	[28]
Gastric neoplasm	DISOKN4Y	Limited	Genetic Variation	[29]
Hamartoma	DIS0I87H	Limited	Biomarker	[30]
High blood pressure	DISY2OHH	Limited	Genetic Variation	[31]
Pneumothorax	DISP86H1	Limited	Biomarker	[32]
Pulmonary disease	DIS6060I	Limited	Genetic Variation	[33]
Thyroid cancer	DIS3VLDH	Limited	Genetic Variation	[18]
Thyroid tumor	DISLVKMD	Limited	Genetic Variation	[18]

3 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 Folliculin (FLCN).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Folliculin (FLCN).	[49]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Folliculin (FLCN).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Folliculin (FLCN).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Folliculin (FLCN).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Folliculin (FLCN).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Folliculin (FLCN).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Folliculin (FLCN).	[39]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Folliculin (FLCN).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Folliculin (FLCN).	[41]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Folliculin (FLCN).	[42]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Folliculin (FLCN).	[40]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Folliculin (FLCN).	[43]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Folliculin (FLCN).	[44]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Folliculin (FLCN).	[45]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Folliculin (FLCN).	[46]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Folliculin (FLCN).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Folliculin (FLCN).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Folliculin (FLCN).	[50]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Folliculin (FLCN).	[51]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Folliculin (FLCN).	[52]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Folliculin (FLCN).	[53]
Manganese	DMKT129	Investigative	Manganese increases the expression of Folliculin (FLCN).	[54]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Folliculin (FLCN).	[55]

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] Pulmonary Neoplasms in Patients with Birt-Hogg-Dub Syndrome: Histopathological Features and Genetic and Somatic Events.PLoS One. 2016 Mar 14;11(3):e0151476. doi: 10.1371/journal.pone.0151476. eCollection 2016.
• [3] Epithelial folliculin enhances airway inflammation in aspirin-exacerbated respiratory disease.Clin Exp Allergy. 2018 Nov;48(11):1464-1473. doi: 10.1111/cea.13253. Epub 2018 Sep 18.
• [4] Association between Birt Hogg Dube syndrome and cancer predisposition.Anticancer Res. 2010 Mar;30(3):751-7.
• [5] Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.PLoS One. 2013 Jul 29;8(7):e70030. doi: 10.1371/journal.pone.0070030. Print 2013.
• [6] Birt-Hogg-Dube Syndrome with a Novel Mutation in the FLCN Gene.Genet Test Mol Biomarkers. 2017 Oct;21(10):632-634. doi: 10.1089/gtmb.2017.0070. Epub 2017 Aug 14.
• [7] Mutations of the Birt-Hogg-Dub (BHD) gene in sporadic colorectal carcinomas and colorectal carcinoma cell lines with microsatellite instability.J Med Genet. 2003 May;40(5):364-7. doi: 10.1136/jmg.40.5.364.
• [8] Characterization of a splice-site mutation in the tumor suppressor gene FLCN associated with renal cancer.BMC Med Genet. 2017 May 12;18(1):53. doi: 10.1186/s12881-017-0416-5.
• [9] 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.
• [10] Renal transplantation in Birt-Hogg-Dub syndrome: should we?.BMC Nephrol. 2018 Oct 16;19(1):267. doi: 10.1186/s12882-018-1064-5.
• [11] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [12] Loss of TP53 in sarcomas with 17p12 to approximately p11 gain. A fine-resolution oligonucleotide array comparative genomic hybridization study.Cytogenet Genome Res. 2007;116(3):153-7. doi: 10.1159/000098180.
• [13] Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation.J Bone Miner Res. 2018 Oct;33(10):1785-1798. doi: 10.1002/jbmr.3477. Epub 2018 Jun 26.
• [14] Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dub syndrome.Cancer Cell. 2002 Aug;2(2):157-64. doi: 10.1016/s1535-6108(02)00104-6.
• [15] Definition of a critical genetic interval related to kidney abnormalities in the Potocki-Lupski syndrome.Am J Med Genet A. 2012 Jul;158A(7):1579-88. doi: 10.1002/ajmg.a.35399. Epub 2012 May 25.
• [16] Folliculin mutations are not associated with severe COPD.BMC Med Genet. 2008 Dec 30;9:120. doi: 10.1186/1471-2350-9-120.
• [17] Bilateral renal tumors in an adult man with Smith-Magenis syndrome: The role of the FLCN gene.Eur J Med Genet. 2016 Oct;59(10):499-501. doi: 10.1016/j.ejmg.2016.09.005. Epub 2016 Sep 12.
• [18] Case Report of Birt-Hogg-Dub Syndrome: Germline Mutations of FLCN Detected in Patients With Renal Cancer and Thyroid Cancer.Medicine (Baltimore). 2016 May;95(22):e3695. doi: 10.1097/MD.0000000000003695.
• [19] Birt-Hogg-Dub syndrome: a large single family cohort.Respir Res. 2016 Feb 29;17:22. doi: 10.1186/s12931-016-0339-2.
• [20] Renal angiomyolipoma in Birt-Hogg-Dube syndrome: A case study supporting overlap with tuberous sclerosis complex.Am J Med Genet A. 2016 Dec;170(12):3323-3326. doi: 10.1002/ajmg.a.37952. Epub 2016 Sep 19.
• [21] Loss of the Birt-Hogg-Dub gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner.Aging Cell. 2013 Aug;12(4):593-603. doi: 10.1111/acel.12081. Epub 2013 May 15.
• [22] Birt-Hogg-Dub syndrome: novel FLCN frameshift deletion in daughter and father with renal cell carcinomas.Fam Cancer. 2016 Jan;15(1):127-32. doi: 10.1007/s10689-015-9837-5.
• [23] Clinical Features, Genetics and Potential Therapeutic Approaches for Birt-Hogg-Dub Syndrome.Expert Opin Orphan Drugs. 2015;3(1):15-29. doi: 10.1517/21678707.2014.987124. Epub 2014 Nov 29.
• [24] CDK4 Regulates Lysosomal Function and mTORC1 Activation to Promote Cancer Cell Survival.Cancer Res. 2019 Oct 15;79(20):5245-5259. doi: 10.1158/0008-5472.CAN-19-0708. Epub 2019 Aug 8.
• [25] The roles of intrinsic disorder-based liquid-liquid phase transitions in the "Dr. Jekyll-Mr. Hyde" behavior of proteins involved in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.Autophagy. 2017;13(12):2115-2162. doi: 10.1080/15548627.2017.1384889. Epub 2017 Dec 17.
• [26] Epithelial folliculin is involved in airway inflammation in workers exposed to toluene diisocyanate.Exp Mol Med. 2017 Nov 17;49(11):e395. doi: 10.1038/emm.2017.180.
• [27] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [28] Nonsense mutations in folliculin presenting as isolated familial spontaneous pneumothorax in adults.Am J Respir Crit Care Med. 2005 Jul 1;172(1):39-44. doi: 10.1164/rccm.200501-143OC. Epub 2005 Apr 1.
• [29] Birt-Hogg-Dub (BHD) gene mutations in human gastric cancer with high frequency microsatellite instability.Cancer Lett. 2007 Apr 8;248(1):103-11. doi: 10.1016/j.canlet.2006.06.005. Epub 2006 Jul 25.
• [30] Tumor Suppressor Folliculin Regulates mTORC1 through Primary Cilia.J Biol Chem. 2016 May 27;291(22):11689-97. doi: 10.1074/jbc.M116.719997. Epub 2016 Apr 12.
• [31] Birt-Hogg-Dub syndrome caused by a mutation of FLCN gene in a CVST patient: a case report.Int J Neurosci. 2020 May;130(5):438-442. doi: 10.1080/00207454.2019.1691204. Epub 2019 Dec 17.
• [32] The Relevance of Family History Taking in the Detection and Management of Birt-Hogg-Dub Syndrome.Respiration. 2019;98(2):125-132. doi: 10.1159/000498973. Epub 2019 Jul 2.
• [33] Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dub syndrome.Orphanet J Rare Dis. 2017 May 30;12(1):104. doi: 10.1186/s13023-017-0656-7.
• [34] 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.
• [35] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [36] 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.
• [37] 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.
• [38] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [39] 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.
• [40] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [41] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [42] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [43] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [44] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [45] Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy. Chem Biol Interact. 2022 Oct 1;366:110043. doi: 10.1016/j.cbi.2022.110043. Epub 2022 Aug 28.
• [46] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [47] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [48] 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.
• [49] 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.
• [50] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [51] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [52] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [53] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [54] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
• [55] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.