Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach

Gastroenterology. 2012 Jan;142(1):21-24.e7. doi: 10.1053/j.gastro.2011.09.050. Epub 2011 Oct 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Atrophy
  • Chief Cells, Gastric / drug effects*
  • Chief Cells, Gastric / pathology
  • Female
  • Gene Expression Regulation / drug effects
  • Injections, Intraperitoneal
  • Integrases / genetics
  • Lac Operon
  • Male
  • Metaplasia
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Parietal Cells, Gastric / drug effects*
  • Parietal Cells, Gastric / pathology
  • Selective Estrogen Receptor Modulators / administration & dosage
  • Selective Estrogen Receptor Modulators / toxicity*
  • Species Specificity
  • Tamoxifen / administration & dosage
  • Tamoxifen / toxicity*
  • Time Factors


  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Cre recombinase
  • Integrases