Hurwitz A, Sztern M I, Looney G A, Pinson D M, Bauer K D, Kimler B F
Department of Internal Medicine, University of Kansas Medical Center, Kansas City 66160-7321, USA.
Cell Prolif. 1995 Oct;28(10):525-31. doi: 10.1111/j.1365-2184.1995.tb00041.x.
This study was designed to evaluate the effects of hypergastrinaemia induced via suppression of gastric acid by omeprazole on carcinogen-induced colon cancer in rats. The carcinogen methylazoxymethanol (MAM), 30 mg/kg, was administered intraperitoneally at 6-weekly intervals to Sprague-Dawley rats. Four weeks after the last MAM injection, the first daily dose of omeprazole, 40 mg/kg, was given by gastric gavage to one group of rats, and the rest were given buffered methylcellulose vehicle. After 10 weeks of daily omeprazole or vehicle, the rats were anaesthetized with ether, blood samples obtained, and animals sacrificed. Gastrin levels in serum from omeprazole-treated rats were elevated nearly six-fold. DNA and RNA levels in gastric mucosa were unchanged by omeprazole, but protein content was somewhat reduced. No biochemical or histological changes related to omeprazole treatment were observed in normal colon. The number of tumours, tumour volumes, and total tumour burden were not significantly different in colons of vehicle- or omeprazole-treated rats. Analysis by flow cytometry revealed that the S phase fraction was lower in tumour cells from omeprazole-treated animals; and that the frequency of DNA aneuploidy was also reduced. The results indicate that while omeprazole-induced suppression of stomach acid in rats elevates levels of gastrin in serum, it does not substantially alter the biochemical or cellular characteristics of carcinogen-induced colon tumours.
本研究旨在评估通过奥美拉唑抑制胃酸诱导的高胃泌素血症对致癌物诱导的大鼠结肠癌的影响。将30mg/kg致癌物甲基氧化偶氮甲醇（MAM）以6周的间隔腹腔注射给Sprague-Dawley大鼠。在最后一次注射MAM后4周，一组大鼠通过胃管给予每日第一剂40mg/kg的奥美拉唑，其余大鼠给予缓冲甲基纤维素赋形剂。在每日给予奥美拉唑或赋形剂10周后，用乙醚麻醉大鼠，采集血样，并处死动物。奥美拉唑治疗的大鼠血清胃泌素水平升高了近6倍。奥美拉唑对胃黏膜中的DNA和RNA水平没有影响，但蛋白质含量略有降低。在正常结肠中未观察到与奥美拉唑治疗相关的生化或组织学变化。接受赋形剂或奥美拉唑治疗的大鼠结肠中的肿瘤数量、肿瘤体积和总肿瘤负荷没有显著差异。流式细胞术分析显示，奥美拉唑治疗动物的肿瘤细胞中S期比例较低；DNA非整倍体频率也降低。结果表明，虽然奥美拉唑诱导的大鼠胃酸抑制会提高血清胃泌素水平，但它不会实质性改变致癌物诱导的结肠肿瘤的生化或细胞特征。
