Reber H A, Johnson F E, Montgomery C, Carl W R
Surgery. 1977 Jul;82(1):34-41.
Pancreatic secretory abnormalities develop in most persons with pancreatic cancer and have been attributed to ductal obstruction. These experiments investigated whether abnormal secretion results instead from carcinogen-induced changes in the secreting cells. Fifty male Syrian Golden hamsters (40 to 100 grams) received weekly injections of di-isopropyl-nitrosamine (250 mg/kg, subcutaneously), and survivors and age-matched controls were studied after 3.5 to 6.5 months of treatment. Pancreatic secretion was stimulated by secretin or cholecystokinin (2 units/kg, intravenously, as a bolus). After each stimulus four 15-minute collections of pancreatic juice were analyzed for HCO3- and Cl- or total protein, amylase, trypsin, and chymotrypsin. The organs were examined histologically. Pancreatic ductal adenocarcinoma developed in 30% of the animals at 5 months, 56% at 5.5 months, and 100% at 6.5 months. The animals without cancer either had hyperplasia of the duct epithelium or were histologically normal. The histologic appearance of acinar tissue and protein secretion were normal in all groups. The tumors did not obstruct the major ducts. In all treated animals the pancreatic secretory response to secretin was of low volume, low maximal [HCO3-] and HCO3- output, and low [Cl- + HCO3-]; these changes progressed with time. The secretory abnormalities antedated the appearance of the neoplasms and were not caused by obstruction.
大多数胰腺癌患者会出现胰腺分泌异常，这一直被归因于导管阻塞。这些实验研究了异常分泌是否反而源于致癌物诱导的分泌细胞变化。50只雄性叙利亚金仓鼠（40至100克）每周皮下注射二异丙基亚硝胺（250毫克/千克），在治疗3.5至6.5个月后对存活的动物和年龄匹配的对照动物进行研究。用促胰液素或胆囊收缩素（2单位/千克，静脉推注）刺激胰腺分泌。每次刺激后，收集4份15分钟的胰液样本，分析其中的HCO3-、Cl-或总蛋白、淀粉酶、胰蛋白酶和糜蛋白酶。对器官进行组织学检查。在5个月时，30%的动物发生了胰腺导管腺癌；5.5个月时为56%；6.5个月时为100%。没有患癌的动物要么有导管上皮增生，要么组织学正常。所有组的腺泡组织组织学外观和蛋白质分泌均正常。肿瘤未阻塞主要导管。在所有接受治疗的动物中，胰腺对促胰液素的分泌反应表现为低容量、低最大[HCO3-]和HCO3-输出量以及低[Cl- + HCO3-]；这些变化随时间进展。分泌异常先于肿瘤出现，并非由阻塞引起。
