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Among these, polycyclic aromatic compounds (PACs), including sulfur-containing heterocyclic hydrocarbons, have been detected in exposed local wildlife, yet the reproductive toxicity and genotoxicity of this suite of PACs remain largely unexplored. This study examined the effects of dibenzothiophene (DBT) and its alkylated congener, 2,4,7-trimethyldibenzothiophene (2,4,7-DBT), on estradiol (E2) synthesis and metabolism in granulosa cells (SIGCs). Cells were exposed to DBT or 2,4,7-DBT for 24 h at concentrations detected in AOSR wildlife tissues (0, 0.1, 1 and 10 nM). We measured the gene expression of markers involved in E2 synthesis, signaling and metabolism, E2 output via ELISA and E2 metabolite production via HPLC-MS\/MS. Exposure to 2,4,7-DBT, but not DBT, shifted E2 metabolism towards 4-OHE2, a genotoxic E2 metabolite. DNA damage was assessed by \u03b3H2Ax expression, alongside DNA repair (Parp1) and survival markers (pAKT). Interestingly, both DBT and 2,4,7-DBT increased DNA damage and triggered apoptosis via a caspase-independent mechanism. Given the critical role of granulosa cells in steroidogenesis and fertility, these findings highlight the endocrine-disruptive effects of sulfur-containing heterocyclic PACs and their potential to compromise reproductive health in exposed mammals.<\/jats:p>","DOI":"10.3390\/ijms26168004","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T11:41:41Z","timestamp":1755603701000},"page":"8004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sulfur-Containing Heterocyclic Aromatic Hydrocarbons Alter Estrogen Metabolism and Cause DNA Damage and Apoptosis in Granulosa Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1816-3433","authenticated-orcid":false,"given":"Genevieve A.","family":"Perono","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thane","family":"Tomy","sequence":"additional","affiliation":[{"name":"Centre for Oil and Gas Research and Development, University of Manitoba, Winnipeg, MB R3T 2N2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Loudon","sequence":"additional","affiliation":[{"name":"Centre for Oil and Gas Research and Development, University of Manitoba, Winnipeg, MB R3T 2N2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-3740","authenticated-orcid":false,"given":"Laiba","family":"Jamshed","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Garlisi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Lauks","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cielle","family":"Lockington","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celina","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg T.","family":"Tomy","sequence":"additional","affiliation":[{"name":"Centre for Oil and Gas Research and Development, University of Manitoba, Winnipeg, MB R3T 2N2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-637X","authenticated-orcid":false,"given":"James J.","family":"Petrik","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Wildlife and Landscape Science Directorate, Environment and Climate Change Canada, National Wildlife Research Center, Ottawa, ON L1A 0H3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-5325","authenticated-orcid":false,"given":"Alison C.","family":"Holloway","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","first-page":"319","article-title":"History, Overview, and Governance of Environmental Monitoring in the Oil Sands Region of Alberta, Canada","volume":"18","author":"Dunlop","year":"2022","journal-title":"Integr. Environ. Assess. Manag."},{"key":"ref_2","unstructured":"(2024). Alberta Energy Outlook (ST98)."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s10745-019-0059-6","article-title":"Oil Sands Extraction in Alberta, Canada: A Review of Impacts and Processes Concerning Indigenous Peoples","volume":"47","author":"Westman","year":"2019","journal-title":"Hum. Ecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127641","DOI":"10.1016\/j.chemosphere.2020.127641","article-title":"A One-Century Sedimentary Record of N- and S-Polycyclic Aromatic Compounds in the Athabasca Oil Sands Region in Canada","volume":"260","author":"Chibwe","year":"2020","journal-title":"Chemosphere"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1007\/s11270-014-1910-4","article-title":"Polycyclic Aromatic Hydrocarbon Deposition in the Snowpack of the Athabasca Oil Sands Region of Alberta, Canada","volume":"225","author":"Cho","year":"2014","journal-title":"Water Air Soil. Pollut."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.scitotenv.2016.10.062","article-title":"Assessment of Wetland\/Upland Vegetation Communities and Evaluation of Soil-Plant Contamination by Polycyclic Aromatic Hydrocarbons and Trace Metals in Regions near Oil Sands Mining in Alberta","volume":"576","author":"Boutin","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"114863","DOI":"10.1016\/j.envpol.2020.114863","article-title":"Polycyclic Aromatic Compounds (PACs) in the Canadian Environment: Exposure and Effects on Wildlife","volume":"265","author":"Wallace","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/10406638.2014.994071","article-title":"Overview of Polycyclic Aromatic Compounds (PAC)","volume":"35","author":"Achten","year":"2015","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"22346","DOI":"10.1073\/pnas.0912050106","article-title":"Oil Sands Development Contributes Polycyclic Aromatic Compounds to the Athabasca River and Its Tributaries","volume":"106","author":"Kelly","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1021\/acs.estlett.2c00677","article-title":"Transboundary Atmospheric Pollution from Mountaintop Coal Mining","volume":"9","author":"Cooke","year":"2022","journal-title":"Environ. Sci. Technol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11718","DOI":"10.1021\/acs.est.4c02596","article-title":"Mountaintop Removal Coal Mining Contaminates Snowpack across a Broad Region","volume":"58","author":"Cooke","year":"2024","journal-title":"Environ. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1007\/s10653-019-00250-5","article-title":"Health Risks from PAHs and Potentially Toxic Elements in Street Dust of a Coal Mining Area in India","volume":"41","author":"Masto","year":"2019","journal-title":"Environ. Geochem. Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.reprotox.2017.07.012","article-title":"Polycyclic Aromatic Hydrocarbons and Female Reproductive Health: A Scoping Review","volume":"73","author":"Bolden","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1039\/C7EM00125H","article-title":"Endocrine Disrupting Potential of PAHs and Their Alkylated Analogues Associated with Oil Spills","volume":"19","author":"Lee","year":"2017","journal-title":"Environ. Sci. Process Impacts"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.aquatox.2010.09.021","article-title":"Fathead Minnow (Pimephales Promelas) Reproduction Is Impaired in Aged Oil Sands Process-Affected Waters","volume":"101","author":"Kavanagh","year":"2011","journal-title":"Aquat. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Barros, \u00c1., \u00c1lvarez, D., and Velando, A. (2014). Long-Term Reproductive Impairment in a Seabird after the Prestige Oil Spill. Biol. Lett., 10.","DOI":"10.1098\/rsbl.2013.1041"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1515\/reveh-2022-0182","article-title":"Exposure to Polycyclic Aromatic Hydrocarbons and Adverse Reproductive Outcomes in Women: Current Status and Future Perspectives","volume":"39","author":"Rafiee","year":"2024","journal-title":"Rev. Environ. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1158\/0008-5472.CAN-12-3636","article-title":"Glutathione-Deficient Mice Have Increased Sensitivity to Transplacental Benzo[a]Pyrene-Induced Premature Ovarian Failure and Ovarian Tumorigenesis","volume":"73","author":"Lim","year":"2013","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jes.2019.12.015","article-title":"Exposure to Polycyclic Aromatic Hydrocarbons and Risk for Premature Ovarian Failure and Reproductive Hormones Imbalance","volume":"91","author":"Ye","year":"2020","journal-title":"J. Environ. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.reprotox.2010.12.006","article-title":"Effect of in Vitro Exposure to Benzo[a]Pyrene, a Component of Cigarette Smoke, on Folliculogenesis, Steroidogenesis and Oocyte Nuclear Maturation","volume":"31","author":"Sadeu","year":"2011","journal-title":"Reprod. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.reprotox.2012.09.003","article-title":"Endocrine Disruptive Actions of Inhaled Benzo(a)Pyrene on Ovarian Function and Fetal Survival in Fisher F-344 Adult Rats","volume":"34","author":"Archibong","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.toxlet.2019.04.008","article-title":"Compounds of PAH Mixtures Dependent Interaction between Multiple Signaling Pathways in Granulosa Tumour Cells","volume":"310","author":"Zajda","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/em.22261","article-title":"In Utero Exposure to Benzo [a] Pyrene Induces Ovarian Mutations at Doses That Deplete Ovarian Follicles in Mice","volume":"60","author":"Luderer","year":"2019","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"116625","DOI":"10.1016\/j.envpol.2021.116625","article-title":"Alkylated Polycyclic Aromatic Hydrocarbons Are the Largest Contributor to Polycyclic Aromatic Compound Concentrations in Traditional Foods of the Bigstone Cree Nation in Alberta, Canada","volume":"275","author":"Golzadeh","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0269-7491(94)90103-1","article-title":"Polycyclic Aromatic Compounds in Northwest Atlantic COD (Gadus Morhua)","volume":"84","author":"Hellou","year":"1994","journal-title":"Environ. Pollut."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"140959","DOI":"10.1016\/j.scitotenv.2020.140959","article-title":"Polycyclic Aromatic Compounds (PACs) and Trace Elements in Four Marine Bird Species from Northern Canada in a Region of Natural Marine Oil and Gas Seeps","volume":"744","author":"Provencher","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/tox.1025","article-title":"Preliminary Risk Assessment of the Wet Landscape Option for Reclamation of Oil Sands Mine Tailings: Bioassays with Mature Fine Tailings Pore Water","volume":"16","author":"Madill","year":"2001","journal-title":"Environ. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.chroma.2012.01.086","article-title":"Qualitative and Quantitative Analysis of Dibenzothiophene, Its Methylated Homologues, and Benzonaphthothiophenes in Crude Oils, Coal, and Sediment Extracts","volume":"1233","author":"Li","year":"2012","journal-title":"J. Chromatogr. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1021\/es505684e","article-title":"First Results from the Oil Sands Passive Air Monitoring Network for Polycyclic Aromatic Compounds","volume":"49","author":"Schuster","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1007\/s10661-023-11846-x","article-title":"Dissolved Polycyclic Aromatic Compounds in Canada\u2019s Athabasca River in Relation to Oil Sands from 2013 through 2019","volume":"195","author":"Roy","year":"2023","journal-title":"Environ. Monit. Assess."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ecoenv.2004.08.002","article-title":"The Effects of Dimethylated and Alkylated Polycyclic Aromatic Hydrocarbons on the Embryonic Development of the Japanese Medaka","volume":"60","author":"Rhodes","year":"2005","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"144703","DOI":"10.1016\/j.scitotenv.2020.144703","article-title":"Thyroid Disrupting Effects of Low-Dose Dibenzothiophene and Cadmium in Single or Concurrent Exposure: New Evidence from a Translational Zebrafish Model","volume":"769","author":"Guzzolino","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s10646-021-02373-x","article-title":"Review of Petroleum Toxicity and Identifying Common Endpoints for Future Research on Diluted Bitumen Toxicity in Marine Mammals","volume":"30","author":"Ruberg","year":"2021","journal-title":"Ecotoxicology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s10661-007-9673-7","article-title":"Levels of Polycyclic Aromatic Hydrocarbons and Dibenzothiophenes in Wetland Sediments and Aquatic Insects in the Oil Sands Area of Northeastern Alberta, Canada","volume":"136","author":"Wayland","year":"2007","journal-title":"Environ. Monit. Assess."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5892","DOI":"10.1021\/es405731j","article-title":"Heterocyclic Aromatic Hydrocarbons Show Estrogenic Activity upon Metabolization in a Recombinant Transactivation Assay","volume":"48","author":"Brinkmann","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/jat.4128","article-title":"Effects of Dibenzothiophene, a Sulfur-containing Heterocyclic Aromatic Hydrocarbon, and Its Alkylated Congener, 2,4,7-trimethyldibenzothiophene, on Placental Trophoblast Cell Function","volume":"41","author":"Perono","year":"2021","journal-title":"J. Appl. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12940-018-0368-z","article-title":"Exploring the Endocrine Activity of Air Pollutants Associated with Unconventional Oil and Gas Extraction","volume":"17","author":"Bolden","year":"2018","journal-title":"Environ. Health"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pescatori, S., Berardinelli, F., Albanesi, J., Ascenzi, P., Marino, M., Antoccia, A., di Masi, A., and Acconcia, F. (2021). A Tale of Ice and Fire: The Dual Role for 17\u03b2-Estradiol in Balancing DNA Damage and Genome Integrity. Cancers, 13.","DOI":"10.3390\/cancers13071583"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1196\/annals.1322.029","article-title":"A Unifying Mechanism in the Initiation of Cancer and Other Diseases by Catechol Quinones","volume":"1028","author":"Cavalieri","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_40","first-page":"4992","article-title":"4-Hydroxy Estrogen Metabolite, Causing Genomic Instability by Attenuating the Function of Spindle-Assembly Checkpoint, Can Serve as a Biomarker for Breast Cancer","volume":"11","author":"Miao","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1073\/pnas.93.8.3294","article-title":"4-Hydroxylation of Estrogens as Marker of Human Mammary Tumors","volume":"93","author":"Liehr","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1093\/carcin\/bgh183","article-title":"Resveratrol Inhibits TCDD-Induced Expression of CYP1A1 and CYP1B1 and Catechol Estrogen-Mediated Oxidative DNA Damage in Cultured Human Mammary Epithelial Cells","volume":"25","author":"Chen","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/978-1-61779-998-3_40","article-title":"Histone H2AX Phosphorylation: A Marker for DNA Damage","volume":"Volume 920","year":"2012","journal-title":"DNA Repair Protocols"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S1016-8478(23)13739-3","article-title":"TRAIL, a Mighty Apoptosis Inducer","volume":"15","author":"Kim","year":"2003","journal-title":"Mol. Cells"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"145403","DOI":"10.1016\/j.scitotenv.2021.145403","article-title":"A Review of Human and Animals Exposure to Polycyclic Aromatic Hydrocarbons: Health Risk and Adverse Effects, Photo-Induced Toxicity and Regulating Effect of Microplastics","volume":"773","author":"Sun","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.chemosphere.2018.10.050","article-title":"Identification of Halogenated Polycyclic Aromatic Hydrocarbons in Biological Samples from Alberta Oil-Sands Region","volume":"215","author":"Xia","year":"2019","journal-title":"Chemosphere"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1073\/pnas.1217675110","article-title":"Legacy of a Half Century of Athabasca Oil Sands Development Recorded by Lake Ecosystems","volume":"110","author":"Kurek","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/humrep\/det439","article-title":"In Vivo Exposure to Benzo(a)Pyrene Induces Significant DNA Damage in Mouse Oocytes and Cumulus Cells","volume":"29","author":"Einaudi","year":"2014","journal-title":"Human Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.taap.2013.08.013","article-title":"7,12-Dimethylbenz[a]Anthracene Exposure Induces the DNA Repair Response in Neonatal Rat Ovaries","volume":"272","author":"Ganesan","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/humrep\/del487","article-title":"Follicle Growth Is Inhibited by Benzo-[a]-Pyrene, at Concentrations Representative of Human Exposure, in an Isolated Rat Follicle Culture Assay","volume":"22","author":"Neal","year":"2007","journal-title":"Human Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yazawa, T., Islam, M.S., Imamichi, Y., Watanabe, H., Yaegashi, K., Ida, T., Sato, T., Kitano, T., Matsuzaki, S., and Umezawa, A. (2023). Comparison of Placental HSD17B1 Expression and Its Regulation in Various Mammalian Species. Animals, 13.","DOI":"10.3390\/ani13040622"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1210\/en.2008-0541","article-title":"Transcription of Steroidogenic Acute Regulatory Protein in the Rodent Ovary and Placenta: Alternative Modes of Cyclic Adenosine 3\u2032, 5\u2032-Monophosphate Dependent and Independent Regulation","volume":"150","author":"Sher","year":"2009","journal-title":"Endocrinology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev.pharmtox.39.1.103","article-title":"Induction of Cytochrome P4501A1","volume":"39","author":"Whitlock","year":"1999","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s11356-011-0483-7","article-title":"Some Heterocyclic Aromatic Compounds Are Ah Receptor Agonists in the DR-CALUX Assay and the EROD Assay with RTL-W1 Cells","volume":"18","author":"Hinger","year":"2011","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"162924","DOI":"10.1016\/j.scitotenv.2023.162924","article-title":"Benzo [b] Naphtho [d] Thiophenes and Naphthylbenzo [b] Thiophenes: Their Aryl Hydrocarbon Receptor-Mediated Activities and Environmental Presence","volume":"879","author":"Ciganek","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1002\/etc.4087","article-title":"Methylated PACs Are More Potent than Their Parent Compounds: A Study of Aryl Hydrocarbon Receptor-Mediated Activity, Degradability, and Mixture Interactions in the H4IIE- Luc Assay: Methylated PACs Are More Potent than Their Parent Compounds","volume":"37","author":"Lam","year":"2018","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.steroids.2014.08.003","article-title":"Estrogen Metabolites and Breast Cancer","volume":"99","author":"Santen","year":"2015","journal-title":"Steroids"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.taap.2005.01.010","article-title":"4-Hydroxyestradiol Induces Oxidative Stress and Apoptosis in Human Mammary Epithelial Cells: Possible Protection by NF-\u03baB and ERK\/MAPK","volume":"208","author":"Chen","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3123\/jemsge.34.129","article-title":"4-Hydroxyestradiol Induces \u03b3-H2AX in the Presence of an Inhibitor of Catechol-O-Methyltransferase in Human Breast Cancer MCF-7 Cells","volume":"34","author":"Yamazaki","year":"2012","journal-title":"Genes Environ."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/10406630490472473","article-title":"Genotoxic Activity Of Thiophenes On Liver Human Cell Line (HepG2)","volume":"24","author":"Amat","year":"2004","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/carcin\/bgq255","article-title":"Estrogen Receptor \u03b1-Mediated Transcription Induces Cell Cycle-Dependent DNA Double-Strand Breaks","volume":"32","author":"Williamson","year":"2011","journal-title":"Carcinogenesis"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.gpb.2016.05.001","article-title":"Functions of PARylation in DNA Damage Repair Pathways","volume":"14","author":"Wei","year":"2016","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Concei\u00e7\u00e3o, C.J.F., Moe, E., Ribeiro, P.A., and Raposo, M. (2025). PARP1: A Comprehensive Review of Its Mechanisms, Therapeutic Implications and Emerging Cancer Treatments. Biochim. Biophys. Acta Rev. Cancer, 1880.","DOI":"10.1016\/j.bbcan.2025.189282"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4162\/nrp.2009.3.3.185","article-title":"Modulatory Effects of \u03b1- and \u03b3-Tocopherols on 4-Hydroxyestradiol Induced Oxidative Stresses in MCF-10A Breast Epithelial Cells","volume":"3","author":"Lee","year":"2009","journal-title":"Nutr. Res. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Mart\u00ed, J.M., Garcia-Diaz, A., Delgado-Bellido, D., O\u2019Valle, F., Gonz\u00e1lez-Flores, A., Carlevaris, O., Rodr\u00edguez-Vargas, J.M., Am\u00e9, J.C., Dantzer, F., and King, G.L. (2021). Selective Modulation by PARP-1 of HIF-1\u03b1-Recruitment to Chromatin during Hypoxia Is Required for Tumor Adaptation to Hypoxic Conditions. Redox Biol., 41.","DOI":"10.1016\/j.redox.2021.101885"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.taap.2003.12.002","article-title":"4-Hydroxy Estradiol but Not 2-Hydroxy Estradiol Induces Expression of Hypoxia-Inducible Factor 1\u03b1 and Vascular Endothelial Growth Factor A through Phosphatidylinositol 3-Kinase\/Akt\/FRAP Pathway in OVCAR-3 and A2780-CP70 Human Ovarian Carcinoma Cells","volume":"196","author":"Gao","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"aad6872","DOI":"10.1126\/science.aad6872","article-title":"A Nuclease That Mediates Cell Death Induced by DNA Damage and Poly(ADP-Ribose) Polymerase-1","volume":"354","author":"Wang","year":"2016","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/15287394.2017.1314840","article-title":"Neurotoxicity of Alkylated Polycyclic Aromatic Compounds in Human Neuroblastoma Cells","volume":"80","author":"Sarma","year":"2017","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/excr.1995.1157","article-title":"Involvement of P53 Expression in cAMP-Mediated Apoptosis in Immortalized Granulosa Cells","volume":"218","author":"Suh","year":"1995","journal-title":"Exp. Cell Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/S0006-2952(03)00485-4","article-title":"Alternative Pathways of Ovarian Apoptosis: Death for Life","volume":"66","author":"Amsterdam","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_71","unstructured":"Ballachey, B.E., and Kloecker, K.A. (1997). Hydrocarbons in Hair, Livers and Intestines of Sea Otters (Enhydra Lurris) Found Dead along the Path of the Exxon Valdez Oil Spill."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.chroma.2018.10.030","article-title":"Comprehensive Two-Dimensional Gas Chromatography High-Resolution Mass Spectrometry for the Analysis of Substituted and Unsubstituted Polycyclic Aromatic Compounds in Environmental Samples","volume":"1579","author":"Idowu","year":"2018","journal-title":"J. Chromatogr. A"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"128920","DOI":"10.1016\/j.chemosphere.2020.128920","article-title":"Co-Exposures to Trace Elements and Polycyclic Aromatic Compounds (PACs) Impacts North American River Otter (Lontra canadensis) Baculum","volume":"265","author":"Thomas","year":"2021","journal-title":"Chemosphere"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Maloy, A., Alexander, S., Andreas, A., Nyunoya, T., and Chandra, D. (2022). Stain-Free Total-Protein Normalization Enhances the Reproducibility of Western Blot Data. Anal. Biochem., 654.","DOI":"10.1016\/j.ab.2022.114840"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jneumeth.2008.05.003","article-title":"The Use of Total Protein Stains as Loading Controls: An Alternative to High-Abundance Single-Protein Controls in Semi-Quantitative Immunoblotting","volume":"172","author":"Aldridge","year":"2008","journal-title":"J. Neurosci. Methods"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Prabhu, K.S., Kuttikrishnan, S., Ahmad, N., Habeeba, U., Mariyam, Z., Suleman, M., Bhat, A.A., and Uddin, S. (2024). H2AX: A Key Player in DNA Damage Response and a Promising Target for Cancer Therapy. Biomed. Pharmacother., 175.","DOI":"10.1016\/j.biopha.2024.116663"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1016\/j.envpol.2019.06.015","article-title":"Polycyclic Aromatic Compounds in Urban Air and Associated Inhalation Cancer Risks: A Case Study Targeting Distinct Source Sectors","volume":"252","author":"Jariyasopit","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"125795","DOI":"10.1016\/j.jhazmat.2021.125795","article-title":"Discovery of Emerging Sulfur-Containing PAHs in PM2.5: Contamination Profiles and Potential Health Risks","volume":"416","author":"Zhang","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1248\/bpb.25.145","article-title":"Estrogenic Activities of Chemicals in Diesel Exhaust Particles","volume":"25","author":"Mori","year":"2002","journal-title":"Biol. Pharm. Bull."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8004\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:30:52Z","timestamp":1760034652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":80,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26168004"],"URL":"https:\/\/doi.org\/10.3390\/ijms26168004","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,19]]}}}