Effect of chronic cimetidine ingestion on fundic and antral epithelial proliferation in the rat.

Recent reports of the association of cimetidine treatment with the development of gastric carcinoma stimulated us to study the effect of chronic cimetidine ingestion on epithelial proliferation in the stomach of male Wistar/Lewis rats. One group of rats received cimetidine in the drinking water to deliver 150-200 mg/kg/day. Control rats received plain water. To label proliferating cells, the rats were injected by tail vein with tritiated thymidine 1 hr before sacrifice at 1, 6, and 12 months. Sections of fundus and antrum were processed for light autoradiography. We found no histological evidence for malignant change and no effect on the measurements of epithelial proliferation by cimetidine in either fundus or antrum at any of the times studied, with the possible exception of an upward shift in the distribution of labeled cells within the proliferative zone of the fundus after 6 months. Thus, under the conditions of our experiments we have been unable to identify an effect of cimetidine on epithelial proliferation which would implicate it as a chemical carcinogen.