title: Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach.
abstract: Tamoxifen, a selective estrogen receptor modulator, is widely used in research and clinically in patients. We find that treatment of normal mice with a single ≥3 mg/20 g body weight dose of tamoxifen leads to apoptosis of >90% of all gastric parietal cells (PCs) and metaplasia of zymogenic chief cells within 3 days. Remarkably, gastric histology returns to nearly normal by 3 weeks. Tamoxifen toxicity occurs by oral and intraperitoneal administration, in both sexes, in multiple strains, and does not depend on estrogen, though acid secretion inhibition is partially protective. Thus, substantial gastric toxicity is a heretofore unappreciated tamoxifen side effect.
authors: Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors: Won Jae
authors: WJ
authors: Huh
authors: Shradha S
authors: SS
authors: Khurana
authors: Jessica H
authors: JH
authors: Geahlen
authors: Kavita
authors: K
authors: Kohli
authors: Rachel A
authors: RA
authors: Waller
authors: Jason C
authors: JC
authors: Mills
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001284:Atrophy; D019872:Chief Cells, Gastric / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D019426:Integrases / Q000235:genetics; D007763:Lac Operon; D008297:Male; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000473:pathology; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000633:toxicity*; D013045:Species Specificity; D013629:Tamoxifen / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
chemical_list: D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases