Rapid induction of enterochromaffinlike cell tumors by histamine2-receptor blockade.

• The effect of acid inhibition on gastric endocrine cells was investigated in Praomys (Mastomys) natalensis. Long-term treatment (1 to 32 weeks) with an irreversible histamine 2-receptor blocker (loxtidine) caused a sustained increase in plasma gastrin levels, which was accompanied by a gradual increase in histamine and histidine decarboxylase activity of the gastric oxyntic mucosa. The density of endocrine cells in the oxyntic mucosa increased gradually, doubled by 8 weeks, and was three times that of controls after 24 weeks of treatment. Hyperplastic changes in the endocrine cell population were evident after 2 to 8 weeks in all animals, whereas dysplastic or neoplastic lesions were observed in half the animals after 16, 24, and 32 weeks of treatment. Gross tumors in the oxyntic mucosa were observed in 1/4 of the animals treated for 24 or 32 weeks. Proliferating cells were identified as enterochromaffinlike cells because they were argyrophilic and immunopositive for chromogranin A and histamine. The results demonstrate that histamine 2-receptor blockade initiated by loxtidine promotes a rapid development of enterochromaffinlike cell tumors in Mastomys and suggest a critical role for gastrin in the formation of these tumors. However, the rate and frequency by which carcinoid tumors appeared in Mastomys after acid inhibition was much greater than that reported in other species, indicating that several factors, including hormonal and genetic factors, are important in the development of gastric endocrine tumors.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Nyckelord

Animals

Chromogranins

metabolism

Dose-Response Relationship

Drug

Endocrine Gland Neoplasms

chemically induced

metabolism

pathology

Endocrine Glands

metabolism

pathology

Enterochromaffin Cells

metabolism

pathology

Histamine

metabolism

Histamine H2 Antagonists

Muridae

Reference Values

Silver

Stomach Neoplasms

chemically induced

metabolism

pathology

Triazoles

administration & dosage

pharmacology

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