Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Free Full Text (Free PDF) Free
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Betton, G. R.
Right arrow Articles by Buckley, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Betton, G. R.
Right arrow Articles by Buckley, P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Journal Article

Gastric ECL-Cell Hyperplasia and Carcinoids in Rodents Following Chronic Administration of H2-Antagonists SK&F 93479 and Oxmetidine and Omeprazole

Graham R. Betton

Smith Kline & French Research Ltd., The Frythe, Welwyn, Hertfordshire, England and Smith Kline & French Laboratories, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939

Charles S. Dormer

Smith Kline & French Research Ltd., The Frythe, Welwyn, Hertfordshire, England and Smith Kline & French Laboratories, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939

Terry Wells

Smith Kline & French Research Ltd., The Frythe, Welwyn, Hertfordshire, England and Smith Kline & French Laboratories, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939

Pauline Pert

Smith Kline & French Research Ltd., The Frythe, Welwyn, Hertfordshire, England and Smith Kline & French Laboratories, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939

Carolyn A. Price

Smith Kline & French Research Ltd., The Frythe, Welwyn, Hertfordshire, England and Smith Kline & French Laboratories, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939

Peter Buckley

Smith Kline & French Research Ltd., The Frythe, Welwyn, Hertfordshire, England and Smith Kline & French Laboratories, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939

The histamine H2-receptor antagonist SK&F 93479 induced gastric neuroendocrine (carcinoid) ECL-cell tumor formation in 6/34 male and 8/37 female rats treated for 22-24 months at 1,000 mg/kg/day po. Focal ECL-cell hyperplasia was present in 21/34 males and 15/37 females, with local infiltration through the muscularis mucosae in half these cases. No focal hyperplasias or carcinoids were present after 200 mg/kg/day po treatment. Investigative studies showed evidence for marked and sustained hypergastrinemia increasing on chronic dosing which was capable of restoring gastric acid secretion and pH to near control values. Using morphometric analysis of immunoperoxidase anti-chromogranin A stained sections, a dose-related and time-dependent neuroendocrine ECL-cell hyperplasia was correlated with the sustained elevated hypergastrinemia. A 21-month mouse oncogenicity study showed no focal neuroendocrine cell hyperplasia or carcinoid tumor induction, but a diffuse neuroendocrine cell hyperplasia and an increase in multifocal glandular hyperplasia of the oxyntic mucosa was observed in mice treated with 1,000 mg/kg SK&F 93479 po. The morphological changes observed in both rat and mouse were considered to be secondary to the hypergastrinemia resulting from the pharmacological suppression of gastric acid secretion by SK&F 93479. These changes were also observed to a more marked degree following omeprazole treatment and were only slight following oxmetidine treatment in the rat.

Toxicologic Pathology, Vol. 16, No. 2, 288-298 (1988)
DOI: 10.1177/019262338801600222
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?