ECL-cell derived gastric cancer in male cotton rats dosed with the H2-blocker loxtidine

被引:30
作者
Fossmark, R
Martinsen, TC
Bakkelund, KE
Kawase, S
Waldum, HL
机构
[1] Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway
[2] St Olavs Hosp, Dept Surg, Trondheim, Norway
[3] Hokkaido Inst Publ Hlth, Div Expt Anim, Sapporo, Hokkaido, Japan
关键词
D O I
10.1158/0008-5472.CAN-03-3647
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Spontaneously hypergastrinemic cotton rats (Sigmodon hispidus) develop tumors that have the phenotype of an adenocarcinoma but most likely originate from the enterochromaffin-like (ECL) cells. Among inbred animals similar to50% of the females, but <1% of males develop spontaneous gastric carcinomas. Gastrin is the principle carcinogen in this model, as >4 months of hypergastrinemia results in carcinoma, but a gastrin receptor antagonist prevents carcinomas. Carcinomas can also be induced by partial corpectomy. In the present study, the insurmountable H2-receptor antagonist loxtidine (200 mg/kg/day) was given to male cotton rats for 6 months. The loxtidine-dosed animals developed hypergastrinemia, whereas control animals remained normogastrinemic. At termination, 4 of 5 cotton rats had cancer located to the oxyntic mucosa, whereas 1 animal had dysplasia. The gastric mucosa of all of the control animals was normal. In the dysplastic mucosa of loxtidine-dosed animals there was a marked increase in chromogranin A-positive cells, where numerous groups of cells also stained positive with the Sevier-Munger technique. In areas of high proliferation and cancer there were also histidine decarboxylase, chromogranin A, and Sevier-Munger-positive cells, altogether indicating an ECL cell origin of the tumors. This represents an interesting animal model where ECL cell-derived gastric cancer can be induced by pharmacological acid inhibition in 6 months.
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页码:3687 / 3693
页数:7
相关论文
共 42 条
[1]
BIOTIN AMPLIFICATION OF BIOTIN AND HORSERADISH-PEROXIDASE SIGNALS IN HISTOCHEMICAL STAINS [J].
ADAMS, JC .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1992, 40 (10) :1457-1463
[2]
BILCHIK AJ, 1989, SURGERY, V106, P1119
[3]
Blumenfeld W, 1996, ARCH PATHOL LAB MED, V120, P478
[4]
EFFECTS OF LOXTIDINE, A NEW HISTAMINE H2-RECEPTOR ANTAGONIST, ON 24-HOUR GASTRIC-SECRETION IN MAN [J].
BOYD, EJS ;
WORMSLEY, KG .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1984, 26 (04) :443-447
[5]
Specificity controls for immunocytochemical methods [J].
Burry, RW .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2000, 48 (02) :163-165
[6]
Spontaneous ECLomas in cotton rats (Sigmodon hispidus):: tumours occurring in hypoacidic/hypergastrinaemic animals with normal parietal cells [J].
Cui, GL ;
Qvigstad, G ;
Falkmer, S ;
Sandvik, AK ;
Kawase, S ;
Waldum, HL .
CARCINOGENESIS, 2000, 21 (01) :23-27
[7]
Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia [J].
Eissele, R ;
Brunner, G ;
Simon, B ;
Solcia, E ;
Arnold, R .
GASTROENTEROLOGY, 1997, 112 (03) :707-717
[8]
Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue [J].
Fossmark, R ;
Martinsen, TC ;
Torp, SH ;
Kawase, S ;
Sandvik, AK ;
Waldum, HL .
ENDOCRINE-RELATED CANCER, 2004, 11 (01) :149-160
[9]
FOSSMARK R, 2004, IN PRESS SCAND J GAS
[10]
INVESTIGATIONS INTO THE GENOTOXIC POTENTIAL OF LOXTIDINE, A LONG-ACTING H-2-RECEPTOR ANTAGONIST [J].
GATEHOUSE, D ;
WEDD, DJ ;
PAES, D ;
DELOW, G ;
BURLINSON, B ;
PASCOE, S ;
BRICE, A ;
STEMP, G ;
TWEATS, DJ .
MUTAGENESIS, 1988, 3 (01) :57-68