Morphologic stomach findings in rats and mice treated with the H2 receptor antagonists, ICI 125,211 and ICI 162,846.
The gross and histopathologic findings seen in the stomachs of rats and mice treated with 2 different H2 receptor antagonists are presented. Studies with the first drug, ICI 125,211, elicited dysplasia/carcinoma lesions in 17 of 828 treated rats with 12 of the 17 lesions occurring in the pyloric region of the stomach. No tumors occurred in mice on study for 18 months. Studies conducted with another drug candidate, ICI 162,846, produced neuroendocrine carcinomas in the stomach of rats and mice. Twenty-five rats out of 312 treated male and female rats had neuroendocrine carcinomas in the gastric fundus with a higher tumor incidence in females. In a 24-month mouse study with ICI 162,846, 45 of 300 treated mice developed neuroendocrine carcinomas in the gastric fundus with a higher incidence in males.
D000818:Animals; D002273:Carcinogens; D002927:Cimetidine / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011720:Pyrazoles / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology
D002273:Carcinogens; D006635:Histamine H2 Antagonists; D011720:Pyrazoles; D002927:Cimetidine; C049056:ICI 162846; C023990:tiotidine