Pinson D M, Havu N, Sztern M I, Mattsson H, Looney G A, Kimler B F, Hurwitz A
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City.
Gastroenterology. 1995 Apr;108(4):1068-74. doi: 10.1016/0016-5085(95)90204-x.
BACKGROUND/AIMS: Published studies suggest that hypergastrinemia stimulates growth of normal or malignant colon tissue. Other studies dispute these findings. This study was designed to test the hypothesis that hypergastrinemia enhances progression or invasiveness of colon cancer.
Colonic carcinomas were induced in male Sprague-Dawley rats by six weekly intraperitoneal injections of methylazoxymethanol. Four weeks after the last injection of carcinogen, the animals were randomized into four treatment groups, including vehicle control, low- and high-dose omeprazole, and ranitidine. After 10 weeks of treatment, the animals were bled, stomach weights were recorded, and colon tumors were mapped, enumerated, measured, and scored histopathologically by Dukes' classification. Crypt and mucosal heights were determined in colonic mucosa unaffected by tumor.
Drug administration induced a sustained hypergastrinemia that did not enhance tumor burden or invasiveness or crypt height/mucosal height ratios. Ranitidine-treated rats consumed less food, weighed less, and developed fewer tumors. This group also had lower crypt and mucosal heights than rats in the vehicle- or omeprazole-treated rats.
The results suggest that endogenous hypergastrinemia induced by these acid-suppressing drugs has no stimulatory effect on colon mucosal growth or progression or biological behavior of experimental rat colon cancer.
背景/目的：已发表的研究表明，高胃泌素血症会刺激正常或恶性结肠组织的生长。其他研究对这些发现提出质疑。本研究旨在验证高胃泌素血症会增强结肠癌进展或侵袭性这一假说。
通过每周一次腹腔注射甲基氧化偶氮甲醇，连续六周，诱导雄性斯普拉格-道利大鼠发生结肠癌。在最后一次注射致癌物四周后，将动物随机分为四个治疗组，包括溶剂对照组、低剂量和高剂量奥美拉唑组以及雷尼替丁组。治疗10周后，采集动物血液，记录胃重量，绘制结肠肿瘤分布图，对肿瘤进行计数、测量，并根据杜克分类法进行组织病理学评分。测定未受肿瘤影响的结肠黏膜隐窝高度和黏膜高度。
给药诱导了持续的高胃泌素血症，但并未增加肿瘤负荷、侵袭性或隐窝高度/黏膜高度比值。雷尼替丁治疗的大鼠食量减少、体重减轻且肿瘤发生较少。该组大鼠的隐窝高度和黏膜高度也低于溶剂或奥美拉唑治疗的大鼠。
结果表明，这些抑酸药物诱导的内源性高胃泌素血症对实验性大鼠结肠癌的结肠黏膜生长、进展或生物学行为没有刺激作用。
