Hypergastrinaemia induced by partial corpectomy results in development of enterochromaffin-like cell carcinoma in male Japanese cotton rats.
BACKGROUND
Among inbred female cotton rats (Sigmodon hispidus) 25%-50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are enterochromaffin-like (ECL)-cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas.


METHODS
Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%-90% of the corpus. A control group was sham-operated.


RESULTS
All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized animals developed gastric cancer. In the dysplastic mucosa surrounding the tumours there was an increase in chromogranin A immunoreactive cells, where numerous cells also were stained using the Sevier-Munger technique. Tumour tissue also contained cells that were chromogranin A positive and stained by Sevier-Munger.


CONCLUSIONS
ECL-cell carcinomas can be induced in male cotton rats by partial corpectomy. This supports a previous statement that spontaneous carcinomas in female cotton rats are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic animals, ECL-cell carcinomas develop independently of gender within a relatively short period of time, and cotton rats therefore represent an interesting model for studying gastric carcinogenesis.
Fossmark
R
R
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim. reidar.fossmark@medisin.ntnu.no
Martinsen
T C
TC
Bakkelund
K E
KE
Kawase
S
S
Torp
S H
SH
Waldum
H L
HL
D000818:Animals; D001707:Biopsy, Needle; D002277:Carcinoma / Q000473:pathology*; D004195:Disease Models, Animal; D019861:Enterochromaffin-like Cells / Q000473:pathology*; D005743:Gastrectomy / Q000379:methods; D005755:Gastrins / Q000097:blood / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008297:Male; D011336:Probability; D051381:Rats; D012680:Sensitivity and Specificity; D016205:Sigmodontinae; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000473:pathology*
D005755:Gastrins