{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:08:16Z","timestamp":1793394496093,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by abnormally elevated pulmonary pressures and right ventricular failure. Excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is one of the most important drivers of vascular remodeling in PAH, for which available treatments have limited effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To gain insights into the mechanisms leading to the development of the disease and identify new actionable targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Protein expression profiling was conducted by two-dimensional liquid chromatography coupled to tandem mass spectrometry in isolated PASMCs from controls and patients with PAH. Multiple molecular, biochemical, and pharmacologic approaches were used to decipher the role of NUDT1 (nudrix hyrolase 1) in PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Increased expression of the detoxifying DNA enzyme NUDT1 was detected in cells and tissues from patients with PAH and animal models. In vitro, molecular or pharmacological inhibition of NUDT1 in PAH-PASMCs induced accumulation of oxidized nucleotides in the DNA, irresolvable DNA damage (comet assay), disruption of cellular bioenergetics (Seahorse), and cell death (terminal deoxynucleotidyl transferase dUTP nick end labeling assay). In two animal models with established PAH (i.e., monocrotaline and Sugen\/hypoxia-treated rats), pharmacological inhibition of NUDT1 using (S)-Crizotinib significantly decreased pulmonary vascular remodeling and improved hemodynamics and cardiac function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results indicate that, by overexpressing NUDT1, PAH-PASMCs hijack persistent oxidative stress in preventing incorporation of oxidized nucleotides into DNA, thus allowing the cell to escape apoptosis and proliferate. Given that NUDT1 inhibitors are under clinical investigation for cancer, they may represent a new therapeutic option for PAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202003-0627oc","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T11:35:04Z","timestamp":1601984104000},"page":"614-627","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":34,"title":["Oxidized DNA Precursors Cleanup by NUDT1 Contributes to Vascular Remodeling in Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"203","author":[{"given":"G\u00e9raldine","family":"Vitry","sequence":"first","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Paulin","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"},{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Grobs","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Claude","family":"Lampron","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsukasa","family":"Shimauchi","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah-Eve","family":"Lemay","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Habbout","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charifa","family":"Awada","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Nadeau","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e","family":"Paradis","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Breuils-Bonnet","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Roux-Dalvai","sequence":"additional","affiliation":[{"name":"Proteomics Platform, Laval University, Qu\u00e9bec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Orcholski","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Potus","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steeve","family":"Provencher","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"},{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Boucherat","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"},{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Research Group, Quebec Heart and Lung Institute Research Centre, Qu\u00e9bec City, Quebec, Canada; and"},{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"2026030322062452200_bib1","doi-asserted-by":"crossref","first-page":"1801887","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur Respir J"},{"key":"2026030322062452200_bib2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S2213-2600(16)00027-8","article-title":"Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis","volume":"4","author":"Lajoie","year":"2016","journal-title":"Lancet Respir Med"},{"key":"2026030322062452200_bib3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1161\/01.RES.0000204572.65400.a5","article-title":"Spatio-temporal diversity of apoptosis within the vascular wall in pulmonary arterial hypertension: heterogeneous BMP signaling may have therapeutic implications","volume":"98","author":"Michelakis","year":"2006","journal-title":"Circ Res"},{"key":"2026030322062452200_bib4","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1172\/JCI86249","article-title":"Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension","volume":"126","author":"Guignabert","year":"2016","journal-title":"J Clin Invest"},{"key":"2026030322062452200_bib5","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1161\/ATVBAHA.112.248500","article-title":"Role of Src tyrosine kinases in experimental pulmonary hypertension","volume":"32","author":"Pullamsetti","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026030322062452200_bib6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/01.CIR.0000102381.57477.50","article-title":"Endothelial dysfunction in pulmonary hypertension","volume":"109","author":"Budhiraja","year":"2004","journal-title":"Circulation"},{"key":"2026030322062452200_bib7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1177\/2045893217701438","article-title":"The cancer theory of pulmonary arterial hypertension","volume":"7","author":"Boucherat","year":"2017","journal-title":"Pulm Circ"},{"key":"2026030322062452200_bib8","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1164\/rccm.201606-1226PP","article-title":"Translational advances in the field of pulmonary hypertension: from cancer biology to new pulmonary arterial hypertension therapeutics. Targeting cell growth and proliferation signaling hubs","volume":"195","author":"Pullamsetti","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030322062452200_bib9","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1183\/09059180.00007513","article-title":"Pathogenesis of pulmonary arterial hypertension: lessons from cancer","volume":"22","author":"Guignabert","year":"2013","journal-title":"Eur Respir Rev"},{"key":"2026030322062452200_bib10","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1183\/13993003.01714-2015","article-title":"The emerging role of epigenetics in pulmonary hypertension","volume":"48","author":"Gamen","year":"2016","journal-title":"Eur Respir J"},{"key":"2026030322062452200_bib11","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.cmet.2014.01.004","article-title":"The metabolic basis of pulmonary arterial hypertension","volume":"19","author":"Sutendra","year":"2014","journal-title":"Cell Metab"},{"key":"2026030322062452200_bib12","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1161\/CIRCULATIONAHA.114.006979","article-title":"Emerging concepts in the molecular basis of pulmonary arterial hypertension: part I: metabolic plasticity and mitochondrial dynamics in the pulmonary circulation and right ventricle in pulmonary arterial hypertension","volume":"131","author":"Ryan","year":"2015","journal-title":"Circulation"},{"key":"2026030322062452200_bib13","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1161\/CIRCULATIONAHA.113.006167","article-title":"Role for DNA damage signaling in pulmonary arterial hypertension","volume":"129","author":"Meloche","year":"2014","journal-title":"Circulation"},{"key":"2026030322062452200_bib14","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1161\/ATVBAHA.119.312537","article-title":"Inhibition of CHK 1 (checkpoint kinase 1) elicits therapeutic effects in pulmonary arterial hypertension","volume":"39","author":"Bourgeois","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026030322062452200_bib15","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1161\/CIRCRESAHA.111.300483","article-title":"Chloroquine prevents progression of experimental pulmonary hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation","volume":"112","author":"Long","year":"2013","journal-title":"Circ Res"},{"key":"2026030322062452200_bib16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature13181","article-title":"MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool","volume":"508","author":"Gad","year":"2014","journal-title":"Nature"},{"key":"2026030322062452200_bib17","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature13194","article-title":"Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy","volume":"508","author":"Huber","year":"2014","journal-title":"Nature"},{"key":"2026030322062452200_bib18","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.freeradbiomed.2016.11.002","article-title":"MTH1 as a nucleotide pool sanitizing enzyme: friend or foe?","volume":"107","author":"Nakabeppu","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"2026030322062452200_bib19","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.117.312579","article-title":"Standards and methodological rigor in pulmonary arterial hypertension preclinical and translational research","volume":"122","author":"Provencher","year":"2018","journal-title":"Circ Res"},{"key":"2026030322062452200_bib20","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026030322062452200_bib21","first-page":"3049","article-title":"Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer","volume":"29","author":"Guzi\u0144ska-Ustymowicz","year":"2009","journal-title":"Anticancer Res"},{"key":"2026030322062452200_bib22","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0002-9440(10)64042-4","article-title":"HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema","volume":"158","author":"Golpon","year":"2001","journal-title":"Am J Pathol"},{"key":"2026030322062452200_bib23","doi-asserted-by":"crossref","first-page":"e007402","DOI":"10.1161\/CIRCIMAGING.117.007402","article-title":"3\u2032-Deoxy-3\u2032-[18F]Fluorothymidine positron emission tomography depicts heterogeneous proliferation pathology in idiopathic pulmonary arterial hypertension patient lung","volume":"11","author":"Ashek","year":"2018","journal-title":"Circ Cardiovasc Imaging"},{"key":"2026030322062452200_bib24","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0002-9440(10)63115-X","article-title":"S100A4\/Mts1 produces murine pulmonary artery changes resembling plexogenic arteriopathy and is increased in human plexogenic arteriopathy","volume":"164","author":"Greenway","year":"2004","journal-title":"Am J Pathol"},{"key":"2026030322062452200_bib25","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat Protoc"},{"key":"2026030322062452200_bib26","doi-asserted-by":"crossref","first-page":"8579","DOI":"10.1074\/jbc.M110566200","article-title":"A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1","volume":"277","author":"Sakai","year":"2002","journal-title":"J Biol Chem"},{"key":"2026030322062452200_bib27","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mrgentox.2010.06.006","article-title":"Programmed cell death triggered by nucleotide pool damage and its prevention by MutT homolog-1 (MTH1) with oxidized purine nucleoside triphosphatase","volume":"703","author":"Nakabeppu","year":"2010","journal-title":"Mutat Res"},{"key":"2026030322062452200_bib28","doi-asserted-by":"crossref","first-page":"37965","DOI":"10.1074\/jbc.M306201200","article-title":"An oxidized purine nucleoside triphosphatase, MTH1, suppresses cell death caused by oxidative stress","volume":"278","author":"Yoshimura","year":"2003","journal-title":"J Biol Chem"},{"key":"2026030322062452200_bib29","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1161\/ATVBAHA.119.313763","article-title":"PIM1 (moloney murine leukemia provirus integration site) inhibition decreases the nonhomologous end-joining DNA damage repair signaling pathway in pulmonary hypertension","volume":"40","author":"Lampron","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026030322062452200_bib30","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1038\/emboj.2009.239","article-title":"FoxM1, a critical regulator of oxidative stress during oncogenesis","volume":"28","author":"Park","year":"2009","journal-title":"EMBO J"},{"key":"2026030322062452200_bib31","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00109-017-1619-0","article-title":"FOXM1 promotes pulmonary artery smooth muscle cell expansion in pulmonary arterial hypertension","volume":"96","author":"Bourgeois","year":"2018","journal-title":"J Mol Med (Berl)"},{"key":"2026030322062452200_bib32","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1164\/rccm.201709-1835OC","article-title":"Endothelial and smooth muscle cell interaction via FoxM1 signaling mediates vascular remodeling and pulmonary hypertension","volume":"198","author":"Dai","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030322062452200_bib33","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nchem.1114","article-title":"The transcription factor FOXM1 is a cellular target of the natural product thiostrepton","volume":"3","author":"Hegde","year":"2011","journal-title":"Nat Chem"},{"key":"2026030322062452200_bib34","doi-asserted-by":"crossref","first-page":"e5592","DOI":"10.1371\/journal.pone.0005592","article-title":"Thiazole antibiotics target FoxM1 and induce apoptosis in human cancer cells","volume":"4","author":"Bhat","year":"2009","journal-title":"PLoS One"},{"key":"2026030322062452200_bib35","doi-asserted-by":"crossref","first-page":"e134885","DOI":"10.1172\/jci.insight.134885","article-title":"MTH1 favors mesothelioma progression and mediates paracrine rescue of bystander endothelium from oxidative damage","volume":"5","author":"Magkouta","year":"2020","journal-title":"JCI Insight"},{"key":"2026030322062452200_bib36","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.celrep.2014.07.037","article-title":"The NF-\u03baB genomic landscape in lymphoblastoid B cells","volume":"8","author":"Zhao","year":"2014","journal-title":"Cell Rep"},{"key":"2026030322062452200_bib37","doi-asserted-by":"crossref","first-page":"10875","DOI":"10.1128\/MCB.25.24.10875-10894.2005","article-title":"Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase","volume":"25","author":"Wang","year":"2005","journal-title":"Mol Cell Biol"},{"key":"2026030322062452200_bib38","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.1158\/0008-5472.CAN-17-1965","article-title":"Skp2-mediated stabilization of MTH1 promotes survival of melanoma cells upon oxidative stress","volume":"77","author":"Wang","year":"2017","journal-title":"Cancer Res"},{"key":"2026030322062452200_bib39","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1038\/sj.onc.1201139","article-title":"Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage","volume":"14","author":"Arai","year":"1997","journal-title":"Oncogene"},{"key":"2026030322062452200_bib40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/978-1-59745-521-3_13","article-title":"Quantitative analysis of oxidized guanine, 8-oxoguanine, in mitochondrial DNA by immunofluorescence method","volume":"554","author":"Ohno","year":"2009","journal-title":"Methods Mol Biol"},{"key":"2026030322062452200_bib41","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S0891-5849(00)00185-4","article-title":"Fluorescence detection of 8-oxoguanine in nuclear and mitochondrial DNA of cultured cells using a recombinant Fab and confocal scanning laser microscopy","volume":"28","author":"Soultanakis","year":"2000","journal-title":"Free Radic Biol Med"},{"key":"2026030322062452200_bib42","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1164\/rccm.201708-1751OC","article-title":"Mitochondrial HSP90 accumulation promotes vascular remodeling in pulmonary arterial hypertension","volume":"198","author":"Boucherat","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030322062452200_bib43","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1128\/MCB.26.6.2093-2108.2006","article-title":"Normal cells, but not cancer cells, survive severe Plk1 depletion","volume":"26","author":"Liu","year":"2006","journal-title":"Mol Cell Biol"},{"key":"2026030322062452200_bib44","first-page":"71","article-title":"Analysis of MTH1 gene function in mice with targeted mutagenesis","volume":"477","author":"Tsuzuki","year":"2001","journal-title":"Mutat Res"},{"key":"2026030322062452200_bib45","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026030322062452200_bib46","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1164\/rccm.201607-1515PP","article-title":"Translating research into improved patient care in pulmonary arterial hypertension","volume":"195","author":"Bonnet","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030322062452200_bib47","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S2213-2600(16)30307-1","article-title":"Initial combination therapy with ambrisentan and tadalafil and mortality in patients with pulmonary arterial hypertension: a secondary analysis of the results from the randomised, controlled AMBITION study","volume":"4","author":"Hoeper","year":"2016","journal-title":"Lancet Respir Med"},{"key":"2026030322062452200_bib48","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1038\/s41467-017-01642-w","article-title":"A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family","volume":"8","author":"Carreras-Puigvert","year":"2017","journal-title":"Nat Commun"},{"key":"2026030322062452200_bib49","first-page":"10888","article-title":"MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP","volume":"46","author":"Jemth","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2026030322062452200_bib50","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1038\/onc.2014.195","article-title":"MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways","volume":"34","author":"Patel","year":"2015","journal-title":"Oncogene"},{"key":"2026030322062452200_bib51","doi-asserted-by":"crossref","first-page":"102644","DOI":"10.1016\/j.dnarep.2019.102644","article-title":"Increased MTH1-specific 8-oxodGTPase activity is a hallmark of cancer in colon, lung and pancreatic tissue","volume":"83","author":"McPherson","year":"2019","journal-title":"DNA Repair (Amst)"},{"key":"2026030322062452200_bib52","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13046-017-0584-3","article-title":"(S)-crizotinib induces apoptosis in human non-small cell lung cancer cells by activating ROS independent of MTH1","volume":"36","author":"Dai","year":"2017","journal-title":"J Exp Clin Cancer Res"},{"key":"2026030322062452200_bib53","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3389\/fgene.2014.00288","article-title":"Comet assay to measure DNA repair: approach and applications","volume":"5","author":"Azqueta","year":"2014","journal-title":"Front Genet"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/203\/5\/614\/67164424\/ajrccm_203_5_614.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/203\/5\/614\/67164424\/ajrccm_203_5_614.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T03:08:26Z","timestamp":1772593706000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/203\/5\/614\/8490981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3,1]]},"published-print":{"date-parts":[[2021,3,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202003-0627oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2021,3,1]]},"assertion":[{"value":"2020-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}