{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:57Z","timestamp":1784557257038,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>\n                    Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants generated from the incomplete combustion of organic material. PAHs have been studied as genotoxicants, but some also act via non-genotoxic mechanisms in estrogen-dependent malignancies, such as breast cancer. PAHs require metabolic activation to electrophilic metabolites to exert their genotoxicity but non-genotoxic properties may also contribute to their carcinogenicity. The role of PAHs in endometrial cancer, a cancer associated with unopposed estrogen action is unknown. We assessed the metabolism of the representative PAH, benzo[\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrene (B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P), to estrogenic compounds in Ishikawa human endometrial cells in the presence and absence of cytochrome P450 induction. Using stable-isotope dilution high-performance liquid chromatography and APCI tandem mass spectrometry in the selected reaction monitoring mode, we analyzed B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P metabolism in Ishikawa cells. Estrogenic activity of B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P metabolites was determined by the endogenous estrogen inducible alkaline phosphatase reporter gene and an exogenous estrogen response element (ERE) luciferase reporter gene construct. We also assessed whether PAHs can induce a proliferative phenotype via estrogen receptor (ER)- and non-ER-regulated pathways. We demonstrate that B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P can be metabolized in human endometrial cells into 3-OH-B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P and B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P-7,8-dione in sufficient amounts to activate ERs. We also show that only B[\n                    <jats:italic>a<\/jats:italic>\n                    ]P-7,8-dione induces endometrial cell proliferation at concentrations lower than required to activate the ER; instead non-genomic signaling by the EGF receptor (EGFR) and activation of the mitogen-activated protein kinase (MAPK) pathway was responsible. This work indicates that human endometrial cells can metabolize PAHs into estrogenic metabolites, which may induce cell proliferation through non-ER-regulated pathways.\n                  <\/jats:p>","DOI":"10.1530\/joe-19-0579","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T05:57:22Z","timestamp":1598421442000},"page":"139-151","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":13,"title":["Estrogen receptor-dependent and independent roles of benzo[a]pyrene in Ishikawa cells"],"prefix":"10.1530","volume":"247","author":[{"given":"Isabelle","family":"Lee","sequence":"first","affiliation":[{"name":"1Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guannan","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"2Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementina","family":"Mesaros","sequence":"additional","affiliation":[{"name":"1Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"2Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor M","family":"Penning","sequence":"additional","affiliation":[{"name":"1Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"2Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/247\/2\/JOE-19-0579.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/247\/2\/JOE-19-0579.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:05Z","timestamp":1784555825000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/247\/2\/139-151\/5354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/joe-19-0579","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11]]}}}