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用N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的大鼠中十二指肠内容物促进胃肿瘤发生

Promotion of gastric tumorigenesis by duodenal contents in rats induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

作者信息

Lehnert T, Deschner E E, Ivankovic S, DeCosse J J

机构信息

Department of Surgery, University of Heidelberg, West Germany.

出版信息

Surgery. 1988 Jun;103(6):643-7.

PMID:3375991
Abstract

Reflux of duodenal contents into the stomach occurs in patients with pyloric incompetence and after gastric resection when bile-diverting procedures are omitted. In such settings duodenal contents have been considered to favor the development of gastric cancer. We have studied the effect of chronic duodenogastric reflux on gastric tumor promotion in rats treated with N-methyl-N'-nitrosoguanidine (MNNG) in an experimental design that avoids physical trauma to the glandular stomach. Thus the effect of trauma-induced tissue repair on carcinogenesis is eliminated, and duodenogastric reflux is isolated as an experimental parameter. To achieve such reflux the first jejunal loop was anastomosed to the forestomach in rats. Animals were exposed to MNNG in drinking water (83 mg/L) for 12 weeks before induction of reflux. Experimental groups were as follow: I, reflux plus MNNG (n = 32); II, MNNG alone (n = 27); III, reflux alone (n = 28); IV, control (n = 25). The experiment was terminated after 56 weeks. Only animals that had survived for 90 days were included in the effective number of animals, which allowed for equal chances of tumor development. In no animal that died earlier had tumors developed. Animals with reflux plus MNNG treatment had significantly more glandular neoplasms (12/32) than did animals with MNNG treatment alone (4/27; p less than 0.05). Similarly, more animals with squamous cell neoplasms were recorded in group I (9/32) than in group II (2/27; p less than 0.05). In consideration of all tumors of epithelial and mesenchymal origin, more gastric malignant tumors were observed in group I (9/32) than in group II (2/27; p less than 0.05). It is concluded that chronic exposure to duodenal contents promotes the development of gastric neoplasia.

摘要

幽门功能不全患者以及胃切除术后未行胆汁转流术的患者会出现十二指肠内容物反流至胃内的情况。在这种情况下,十二指肠内容物被认为有利于胃癌的发生。我们在一项避免对腺胃造成物理创伤的实验设计中,研究了慢性十二指肠-胃反流对经N-甲基-N'-亚硝基胍(MNNG)处理的大鼠胃肿瘤促进作用的影响。这样就消除了创伤诱导的组织修复对致癌作用的影响,并将十二指肠-胃反流作为一个实验参数分离出来。为实现这种反流,将大鼠的空肠第一段与前胃进行吻合。在诱导反流前,动物饮用含MNNG(83 mg/L)的水12周。实验组如下:I组,反流加MNNG(n = 32);II组,仅MNNG(n = 27);III组,仅反流(n = 28);IV组,对照组(n = 25)。56周后实验结束。只有存活90天的动物才被纳入有效动物数量,这使得肿瘤发生的机会均等。没有一只早期死亡的动物发生肿瘤。与仅接受MNNG处理的动物(4/27;p<0.05)相比,接受反流加MNNG处理的动物发生腺性肿瘤的数量显著更多(12/32)。同样,I组记录到的鳞状细胞瘤动物数量(9/32)多于II组(2/27;p<0.05)。考虑到所有上皮和间叶来源的肿瘤,I组观察到的胃恶性肿瘤数量(9/32)多于II组(2/27;p<0.05)。结论是,长期接触十二指肠内容物会促进胃肿瘤的发生。

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1
Promotion of gastric tumorigenesis by duodenal contents in rats induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).用N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的大鼠中十二指肠内容物促进胃肿瘤发生
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Effect of flurbiprofen and 16,16-dimethyl-prostaglandin E2 on gastrointestinal tumorigenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats. I. Squamous epithelium and mesenchymal tissue.氟比洛芬和16,16-二甲基前列腺素E2对N-甲基-N'-硝基-N-亚硝基胍诱导的大鼠胃肠道肿瘤发生的影响。I. 鳞状上皮和间充质组织。
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Study of the promoting effect of sodium chloride on gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine in inbred Wistar rats.氯化钠对近交系Wistar大鼠经N-甲基-N'-硝基-N-亚硝基胍诱发胃癌的促进作用研究。
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Helicobacter pylori is not a co-carcinogen in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis.
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引用本文的文献

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Effect of N-methyl-N'-nitro-N-nitrosoguanidine on carbohydrate profiles of non-metaplastic rat gastric mucosa.N-甲基-N'-硝基-N-亚硝基胍对非化生大鼠胃黏膜碳水化合物谱的影响。
J Cancer Res Clin Oncol. 1993;119(3):155-9. doi: 10.1007/BF01229530.
2
Inhibition of gastric tumorigenesis by alpha-difluoromethylornithine in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.α-二氟甲基鸟氨酸对用N-甲基-N'-硝基-N-亚硝基胍处理的大鼠胃肿瘤发生的抑制作用。
J Cancer Res Clin Oncol. 1993;119(10):594-8. doi: 10.1007/BF01372722.
3
DNA damage in the stomach after vagotomy measured by 32P-postlabelling.
通过³²P后标记法测定迷走神经切断术后胃内的DNA损伤。
Gut. 1993 Dec;34(12):1683-7. doi: 10.1136/gut.34.12.1683.