Appel M J, Meijers M, Van Garderen-Hoetmer A, Lamers C B, Rovati L C, Sprij-Mooij D, Jansen J B, Woutersen R A
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Br J Cancer. 1992 Jul;66(1):46-50. doi: 10.1038/bjc.1992.214.
The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight. Rats treated with cholecystokinin developed more acidophilic atypical acinar cell nodules, adenomas and adenocarcinomas than control animals. Rats maintained on the high-fat diet developed significantly more adenomas and adenocarcinomas than controls given a diet low in unsaturated fat. Lorglumide largely inhibited the enhancing effect of cholecystokinin, but not of dietary fat, on pancreatic carcinogenesis indicating that it is unlikely that the promoting effect of dietary unsaturated fat on pancreatic carcinogenesis is mediated via cholecystokinin.
使用高度特异性的胆囊收缩素受体拮抗剂洛谷胺,在氮杂丝氨酸处理的大鼠中研究了胆囊收缩素在膳食脂肪促进胰腺癌发生中的作用。治疗开始8个月后处死动物。胆囊收缩素而非膳食不饱和脂肪增加了胰腺重量。与对照动物相比,接受胆囊收缩素治疗的大鼠出现了更多嗜酸性非典型腺泡细胞结节、腺瘤和腺癌。维持高脂饮食的大鼠比给予不饱和脂肪含量低的饮食的对照大鼠发生的腺瘤和腺癌明显更多。洛谷胺在很大程度上抑制了胆囊收缩素对胰腺癌发生的促进作用,但未抑制膳食脂肪的促进作用,这表明膳食不饱和脂肪对胰腺癌发生的促进作用不太可能通过胆囊收缩素介导。