{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:20:11Z","timestamp":1762507211754,"version":"3.37.3"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T00:00:00Z","timestamp":1507507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000139","name":"U.S. Environmental Protection Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000139","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,1,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>ATP binding cassette sub\u2010family member 2 (ABCG2) is a well\u2010defined efflux transporter found in a variety of tissues. The role of ABCG2 during early embryonic development, however, is not established. Previous work which compared data from the ToxCast screening program with that from in\u2010house studies suggested an association exists between exposure to xenobiotics that regulate Abcg2 transcription and differentiation of mouse embryonic stem cells (mESC), a relationship potentially related to redox homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>mESC were grown for up to 9 days. Pharmacological inhibitors were used to assess transporter function with and without xenobiotic exposure. Proliferation and differentiation were evaluated using RedDot1 and quantiative reverse transcriptase\u2010polymerase chain reaction, respectively. ABCG2 activity was assessed using a Pheophorbide a\u2010based fluorescent assay. Protein expression was measured by capillary\u2010based immunoassay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ABCG2 activity increased in differentiating mESC. Treatment with K0143, an inhibitor of ABCG2, had no effect on proliferation or differentiation. As expected, mitoxantrone and topotecan, two chemotherapeutics, displayed increased toxicity in the presence of K0143. Exposure to K0143 in combination with chemicals predicted by ToxCast to regulate ABCG2 expression did not alter xenobiotic\u2010induced toxicity. Moreover, inhibition of ABCG2 did not shift the toxicity of either tert\u2010Butyl hydroperoxide or paraquat, two oxidative stressors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As previously reported, ABCG2 serves a protective role in mESC. The role of ABCG2 in regulating redox status, however, was unclear. The hypothesis that ABCG2 plays a fundamental role during mESC differentiation or that regulation of the receptor by xenobiotics may be associated with altered mESC differentiation could not be supported. Birth Defects Research, 110:35\u201347, 2018. Published 2017. This article is a U.S. Government work and is in the public domain in the USA<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1114","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T07:02:48Z","timestamp":1507532568000},"page":"35-47","source":"Crossref","is-referenced-by-count":1,"title":["ATP Binding Cassette Sub\u2010family Member 2 (ABCG2) and Xenobiotic Exposure During Early Mouse Embryonic Stem Cell Differentiation"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4033-8690","authenticated-orcid":false,"given":"Mitchell B.","family":"Rosen","sequence":"first","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory Integrated Systems Toxicology Division Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan C.","family":"Jeffay","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory Integrated Systems Toxicology Division Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harriette P.","family":"Nichols","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory Integrated Systems Toxicology Division Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria R.","family":"Hoopes","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory Integrated Systems Toxicology Division Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"E. Sidney","family":"Hunter","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory Integrated Systems Toxicology Division Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,9]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"335","article-title":"Nrf2\u2010dependent and \u2010independent induction of ABC transporters ABCC1, ABCC2, and ABCG2 in HepG2 cells under oxidative stress","volume":"6","author":"Adachi T","year":"2007","journal-title":"J Exp Ther Oncol"},{"key":"e_1_2_6_3_1","first-page":"417","article-title":"Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C","volume":"1","author":"Allen JD","year":"2002","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0398"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2008.08.010"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.4.2235"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.46582\/jsrm.0801003","article-title":"Derivation of es cells from early stage preimplantation embryos and characterisation of their cardiac differentiation potential in mice","volume":"8","author":"Bag S","year":"2012","journal-title":"J Stem Cells Regen Med"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1242\/dev.117.2.543","article-title":"The mouse NCAM gene displays a biphasic expression pattern during neural tube development","volume":"117","author":"Bally\u2010Cuif L","year":"1993","journal-title":"Development"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2011.01.007"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.090506"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.200011"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010964"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018540"},{"key":"e_1_2_6_14_1","first-page":"894","article-title":"Mouse ES cell\u2010derived cardiac precursor cells are multipotent and facilitate identification of novel cardiac genes","volume":"118","author":"Christoforou N","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_6_15_1","first-page":"117","article-title":"The evolution of vertebrate gastrulation","author":"Robertis EM","year":"1994","journal-title":"Dev Suppl"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.139170"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2010.02.012"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2013.02.009"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-012-0838-0"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1002"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055062"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2013.00138"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/biores.2014.0010"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.4.1797"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707218"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057105284576"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.240341"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.2007.00162.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.10.003"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202607599"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.12.008"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-33-10703.2003"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313599200"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.07.020"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.10.060"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90662-X"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.08.011"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.09.028"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0077"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00393-3"},{"key":"e_1_2_6_42_1","first-page":"1","article-title":"Human ABCG2: structure, function, and its role in multidrug resistance","volume":"3","author":"Mo W","year":"2012","journal-title":"Int J Biochem Mol Biol"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.011.10320"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81769-9"},{"key":"e_1_2_6_45_1","first-page":"945","article-title":"Characterization and localization of side population cells in the lens","volume":"16","author":"Oka M","year":"2010","journal-title":"Mol Vis"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1195"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.2.1440"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2008.11.003"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.07.032"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.03.123"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2005.12.003"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.2.507"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.9.1.105"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-10-0108"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.113.088609"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00009.2003"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004023"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-1033"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604890200"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.065078"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-10-0270"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2008.0391"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2935-13.2014"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.17.2105"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.192"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07783.x"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0901-1028"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1566"}],"container-title":["Birth Defects Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdr2.1114","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdr2.1114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T07:09:08Z","timestamp":1695971348000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdr2.1114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,9]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1,15]]}},"alternative-id":["10.1002\/bdr2.1114"],"URL":"https:\/\/doi.org\/10.1002\/bdr2.1114","archive":["Portico"],"relation":{},"ISSN":["2472-1727","2472-1727"],"issn-type":[{"type":"print","value":"2472-1727"},{"type":"electronic","value":"2472-1727"}],"subject":[],"published":{"date-parts":[[2017,10,9]]}}}