Tsujii M, Kawano S, Tsuji S, Takei Y, Tamura K, Fusamoto H, Kamada T
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Carcinogenesis. 1995 Mar;16(3):563-6. doi: 10.1093/carcin/16.3.563.
Although an association is suggested between gastric cancer and prior infection with Helicobacter pylori (HP), the role of HP in gastric carcinogenesis remains obscure. HP has potent urease activity and produces ammonia, a factor causing HP-related gastroduodenal mucosal lesions. In this study, rats were examined in an effort to determine effects of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After pretreatment with MNNG (83 mg/l) for 24 weeks, a solution of either 0.01% ammonia or plain tap water was administered to the animals as drinking water for an additional 24 weeks. The administration of the 0.01% ammonia solution significantly increased the incidence and number of cancers in the glandular stomach. The numbers of cases in which these cancers penetrated the muscle layer or deeper and of low-grade differentiated adenocarcinomas were significantly higher in rats receiving the ammonia solution. Continuing administration of ammonia accelerated cell proliferation in the gastric mucosa, but had no effect on the serum gastrin level. Therefore, gastric ammonia, which stimulates mucosal cell proliferation, appears to be an important promoter in carcinogenesis in rats and possibly in the HP-related gastric carcinogenesis in humans.
虽然提示胃癌与既往幽门螺杆菌(HP)感染之间存在关联,但HP在胃癌发生中的作用仍不清楚。HP具有强大的脲酶活性并产生氨,这是导致HP相关胃十二指肠黏膜病变的一个因素。在本研究中,对大鼠进行了检查,以确定氨对N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的胃癌发生的影响。在用MNNG(83mg/l)预处理24周后,给动物饮用0.01%氨溶液或普通自来水作为饮用水,持续24周。给予0.01%氨溶液显著增加了腺胃癌症的发生率和数量。接受氨溶液的大鼠中,这些癌症穿透肌层或更深层的病例数以及低分化腺癌的病例数显著更高。持续给予氨可加速胃黏膜细胞增殖,但对血清胃泌素水平无影响。因此,刺激黏膜细胞增殖的胃内氨似乎是大鼠致癌作用以及可能是人类HP相关胃癌发生中的一个重要促进因素。