{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:27:41Z","timestamp":1791325661279,"version":"4.3.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for esophageal adenocarcinoma (EAC). Despite similar rates of GERD and other risk factors across racial groups, EAC progression disproportionately impacts Caucasians. We recently reported that elevated tissue levels of the detoxification enzyme GSTT2 in the esophagi of Blacks compared to Caucasians may contribute protection. Herein, we extend our research to investigate whether cranberry proanthocyanidins (C\u2010PAC) mitigate bile acid\u2010induced damage and GSTT2 levels utilizing a racially diverse panel of patient\u2010derived primary esophageal cultures. We have shown that C\u2010PACs mitigate reflux\u2010induced DNA damage through GSTT2 upregulation in a rat esophageal reflux model, but whether effects are recapitulated in humans or differentially based on race remains unknown. We isolated normal primary esophageal cells from Black and Caucasian patients and assessed GSTT2 protein levels and cellular viability following exposure to a bile acid cocktail with and without C\u2010PAC treatment. Constitutive GSTT2 levels were significantly elevated in Black (2.9\u2010fold) compared to Caucasian patients, as were GSTT2 levels in Black patients with GERD. C\u2010PAC treatment induced GSTT2 levels 1.6\u2010fold in primary normal esophageal cells. GSTT2 induction by C\u2010PAC was greatest in cells with constitutively low GSTT2 expression. Overall, C\u2010PAC mitigated bile\u2010induced reductions of GSTT2 and subsequent loss of cell viability regardless of basal GSTT2 expression or race. These data support that C\u2010PAC may be a safe efficacious agent to promote epithelial fitness through GSTT2 induction and in turn protect against bile acid\u2010induced esophageal injury.<\/jats:p>","DOI":"10.1002\/mc.23369","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T20:42:17Z","timestamp":1636576937000},"page":"281-287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Proanthocyanidins mitigate bile acid\u2010induced changes in GSTT2 levels in a panel of racially diverse patient\u2010derived primary esophageal cell cultures"],"prefix":"10.1002","volume":"61","author":[{"given":"Katherine M.","family":"Weh","sequence":"first","affiliation":[{"name":"Department of Surgery, Section of Thoracic Surgery University of Michigan Ann Arbor Michigan USA"},{"name":"Rogel Comprehensive Cancer Center University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle K.","family":"Turgeon","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H.","family":"Rubenstein","sequence":"additional","affiliation":[{"name":"Rogel Comprehensive Cancer Center University of Michigan Ann Arbor Michigan USA"},{"name":"Division of Gastroenterology, Department of Internal Medicine University of Michigan Ann Arbor Michigan USA"},{"name":"LTC Charles S Kettles Veterans Affairs Medical Center Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology University of Nebraska Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy B.","family":"Howell","sequence":"additional","affiliation":[{"name":"Marucci Center for Blueberry and Cranberry Research Rutgers University Chatsworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Thoracic Surgery University of Michigan Ann Arbor Michigan USA"},{"name":"Rogel Comprehensive Cancer Center University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Kresty","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Thoracic Surgery University of Michigan Ann Arbor Michigan USA"},{"name":"Rogel Comprehensive Cancer Center University of Michigan Ann Arbor Michigan 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