Yamashita Y, Homma K, Kako N, Clark G W, Smyrk T C, Hinder R A, Adrian T E, DeMeester T R, Mirvish S S
Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska, USA.
J Gastrointest Surg. 1998 Jul-Aug;2(4):350-5. doi: 10.1016/s1091-255x(98)80074-7.
When duodenal content is allowed to reflux into the esophagus of nitrosamine-treated rats, esophageal cancer is induced more rapidly and at higher frequency than after carcinogen treatment alone. The purpose of the present study was to identify the components of the duodenal content that are responsible for enhancing esophageal carcinogenesis. Eight-week-old Sprague-Dawley rats underwent one of four operations as follows: diversion of bile alone, pancreatic juice alone, both bile and pancreatic juice into the esophagus, or a control operation with no induced reflux. Two weeks after surgery, rats were treated with the esophageal carcinogen 2, 6-dimethylnitrosomorpholine (48 mg/kg [0.1 of LD50] intraperitoneally weekly for 20 weeks). The rats were killed at age 30 weeks. The esophagus was removed and full-length strips were examined under a microscope; separate segments were taken for flow cytometric evaluation. The prevalence of DNA aneuploidy and histologic esophageal papillomas or squamous cancer was increased in carcinogen-treated rats with pancreatic juice reflux (P <0.05 vs. control) and the combination of pancreatic and bile reflux (P <0.05 vs. control) but not in rats with bile reflux alone. We conclude that pancreatic juice is the most potent component of the duodenal refluxate in the promotion of esophageal carcinogenesis in rats.
当允许十二指肠内容物反流至经亚硝胺处理的大鼠食管时，与单独给予致癌物处理相比，食管癌的诱发速度更快且频率更高。本研究的目的是确定十二指肠内容物中导致食管致癌作用增强的成分。8周龄的斯普拉格-道利大鼠接受以下四种手术之一：单纯胆汁转流、单纯胰液转流、胆汁和胰液均转流入食管，或进行不诱发反流的对照手术。术后两周，大鼠接受食管致癌物2,6-二甲基亚硝基吗啉处理（48 mg/kg[LD50的0.1]，每周腹腔注射一次，共20周）。大鼠在30周龄时处死。取出食管，制作全长切片并在显微镜下检查；取不同节段进行流式细胞术评估。在伴有胰液反流的致癌物处理大鼠（与对照组相比，P<0.05）以及伴有胰液和胆汁反流的大鼠（与对照组相比，P< 0.05）中，DNA非整倍体以及组织学上食管乳头状瘤或鳞状细胞癌的发生率升高，但单纯胆汁反流的大鼠中未出现这种情况。我们得出结论，胰液是十二指肠反流物中促进大鼠食管致癌作用的最有效成分。
