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Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach
Won Jae Huh1, Shradha S Khurana, Jessica H Geahlen
1Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
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.
Insights
Tamoxifen causes significant gastric toxicity, leading to parietal cell apoptosis and chief cell metaplasia in mice. Stomach histology recovers within three weeks, indicating a temporary but severe side effect.
Area of Science:
- Gastroenterology
- Endocrinology
- Toxicology
Background:
- Tamoxifen is a widely used selective estrogen receptor modulator in clinical and research settings.
- Its known side effects typically involve reproductive organs, but gastrointestinal effects are less understood.
Purpose of the Study:
- To investigate the potential gastrointestinal toxicity of tamoxifen.
- To characterize the effects of tamoxifen on gastric histology and cell populations.
Main Methods:
- Normal mice were administered a single high dose of tamoxifen (≥3 mg/20 g body weight) via oral or intraperitoneal routes.
- Gastric histology was examined at 3 days and 3 weeks post-treatment.
- Effects were assessed in both sexes and multiple mouse strains.
Main Results:
- Tamoxifen treatment induced apoptosis in over 90% of gastric parietal cells within 3 days.
- Zymogenic chief cells underwent metaplasia.
- Gastric histology largely recovered to normal by 3 weeks.
- Toxicity was observed across sexes and strains, independent of estrogen, with partial protection by acid secretion inhibition.
Conclusions:
- Substantial gastric toxicity, including parietal cell loss and metaplasia, is a significant and previously unrecognized side effect of tamoxifen.
- The observed gastric damage is transient, with histological recovery within weeks.
- Further research is warranted to understand the mechanisms and clinical implications of tamoxifen-induced gastric toxicity.
