Takahashi A, Tanida N, Kawaura A, Nishikawa M, Shimoyama T
Department of Internal Medicine, Hyogo College of Medicine, Japan.
Eur J Cancer Prev. 1993 Mar;2(2):161-7. doi: 10.1097/00008469-199303000-00009.
Peroral sulpholithocholic acid (SLC) promoted colonic tumorigenesis in conventional rats. We then tested this compound in the mouse, a species with different bile acid metabolism from the rat. Female conventional ICR mice received 0.5 mg of N-methyl-N-nitrosourea (MNU) three times in one week intrarectally or 16 mg/kg body weight of 1,2-dimethylhydrazine (DMH) subcutaneously once a week for 10 weeks, followed by a basal diet (CE-2), or CE-2 containing SLC or lithocholic acid (LC) (both at 0.5 mmol/100 g CE-2) for 40 weeks. At autopsy, numbers of mice bearing colonic neoplasms were 4/26 (15%) in the MNU + CE-2, 4/23 (17%) in the MNU + SLC, 5/28 (18%) in the MNU + LC, 12/24 (50%) in the DMH + CE-2, 6/23 (26%) in the DMH + SLC and 11/27 (41%) in the DMH + LC group. The DMH + SLC group had less adenocarcinomas than did the DMH + CE-2 and the DMH + LC group (P < 0.05). Total faecal bile acids in the mice fed on bile salts showed threefold increases compared with those on the basal diet. Sulphates constituted an average 7% and 19% of faecal bile acids in the MNU + SLC and DMH + SLC group, respectively. These results indicated that effects of peroral SLC on colonic carcinogenesis correlated with the degree of desulphation of SLC in the intestine and sulphates per se inhibited colonic carcinogenesis.
经口给予硫代石胆酸（SLC）可促进常规大鼠的结肠肿瘤发生。随后，我们在小鼠中测试了该化合物，小鼠与大鼠的胆汁酸代谢不同。雌性常规ICR小鼠在一周内直肠内给予0.5mg N-甲基-N-亚硝基脲（MNU）3次，或每周皮下注射16mg/kg体重的1,2-二甲基肼（DMH），持续10周，随后给予基础饮食（CE-2），或含SLC或石胆酸（LC）（均为0.5mmol/100g CE-2）的CE-2饮食，持续40周。尸检时，MNU + CE-2组中发生结肠肿瘤的小鼠数量为4/26（15%），MNU + SLC组为4/23（17%），MNU + LC组为5/28（18%），DMH + CE-2组为12/24（50%），DMH + SLC组为6/23（26%），DMH + LC组为11/27（41%）。DMH + SLC组的腺癌数量少于DMH + CE-2组和DMH + LC组（P < 0.05）。喂食胆盐的小鼠粪便总胆汁酸比基础饮食组增加了三倍。在MNU + SLC组和DMH + SLC组中，硫酸盐分别平均占粪便胆汁酸的7%和19%。这些结果表明，经口给予SLC对结肠致癌作用与SLC在肠道中的脱硫程度相关，且硫酸盐本身可抑制结肠致癌作用。
