{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:46:20Z","timestamp":1777081580552,"version":"3.51.4"},"reference-count":75,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pancreatic cancer is the fourth leading cause of cancer deaths in the US and predicted to rise to second by 2030. Several risk factors have been identified as potential contributors to pancreatic cancer development including lifestyle factors and long\u2010term exposure to occupational and environmental carcinogens. In mice, exposure to perfluorooctanoic acid (PFOA) leads to diabetic outcomes and pancreatic cancer, while epidemiologic studies have linked PFOA exposure to type 1, type 2, and gestational diabetes, obesity, and pancreatic cancer. While multiple studies have evaluated changes in serum lipid levels in association with PFOA exposure, none to date have evaluated PFOA\u2010associated lipid alterations in the pancreas. Using the LSL\u2010KRas\n                    <jats:sup>G12D<\/jats:sup>\n                    ; Pdx\u20101\u2010Cre (KC) mouse model of pancreatic cancer, we report upregulation of lipid species within the acylcarnitine (CAR) and ceramide (Cer) lipid groups and downregulation of lipids in the phosphatidylcholine, phosphatidylethanolamine (PE), and phosphatidylserine groups following exposure to 1 and 5\u2009ppm PFOA for 6\u2009months. The most upregulated lipids following PFOA exposure included individual Cer and CAR species while PE species comprised the top group of downregulated lipids. Thromboxane B2 (TXB2), a proinflammatory eicosanoid, was the most upregulated lipid in the 1 and 5\u2009ppm KC treatment groups with a fold\u2010change of ~12\u2010fold and ~31\u2010fold in the 1 and 5\u2009ppm KC treatment groups, respectively. As these lipid alterations have been linked to mitochondrial dysfunction, obesity, and inflammation, our results suggest that PFOA\u2010induced lipid alterations may be involved in adverse health outcomes including diabetes and pancreatic cancer.\n                  <\/jats:p>","DOI":"10.1002\/tox.70109","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:29:31Z","timestamp":1777080571000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PFOA<\/scp>\n                    Exposure Elicits Quantitative Lipidomic Changes in the Pancreas in a Mouse Model of Pancreatic Cancer"],"prefix":"10.1002","author":[{"given":"Barbara A.","family":"Hocevar","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health School of Public Health, Indiana University  Bloomington Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0162-0338","authenticated-orcid":false,"given":"Lisa M.","family":"Kamendulis","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health School of Public Health, Indiana University  Bloomington Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.envint.2019.04.067","article-title":"Carcinogenicity Assessment: Addressing the Challenges of Cancer and Chemicals in the Environment","volume":"128","author":"Madia F.","year":"2019","journal-title":"Environment International"},{"issue":"6","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1053\/j.gastro.2013.01.068","article-title":"The Epidemiology of Pancreatitis and Pancreatic Cancer","volume":"144","author":"Yadav D.","year":"2013","journal-title":"Gastroenterology"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1007\/s00204-016-1821-9","article-title":"Environmental Risk Factors for Pancreatic Cancer: An Update","volume":"90","author":"Barone E.","year":"2016","journal-title":"Archives of Toxicology"},{"issue":"9612","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0140-6736(08)60269-X","article-title":"Body\u2010Mass Index and Incidence of Cancer: A Systematic Review and Meta\u2010Analysis of Prospective Observational Studies","volume":"371","author":"Renehan A. 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B.","year":"2001","journal-title":"Toxicological Sciences"},{"key":"e_1_2_10_11_1","unstructured":"\u201cNational Toxicology Program: NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Carboxylates (Perfluorohexanoic Acid Perfluorooctanoic Acid Perfluorononanoic Acid and Perfluorodecanoic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats \u201dToxicity Report 97. Research Triangle Park NC: National Toxicology Program 2019."},{"issue":"5","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/carcin\/bgac005","article-title":"Exposure to Perfluorooctanoic Acid Leads to Promotion of Pancreatic Cancer","volume":"43","author":"Kamendulis L. 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