Sulphated bile acid per se inhibits colonic carcinogenesis in mice.
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.
Takahashi
A
A
Department of Internal Medicine, Hyogo College of Medicine, Japan.
Tanida
N
N
Kawaura
A
A
Nishikawa
M
M
Shimoyama
T
T
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000473:pathology; D000236:Adenoma / Q000473:pathology; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis; D002273:Carcinogens / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002793:Cholic Acids / Q000032:analysis; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D003840:Deoxycholic Acid / Q000032:analysis; D004127:Dimethylhydrazines / Q000008:administration & dosage / Q000009:adverse effects; D005243:Feces / Q000737:chemistry; D005260:Female; D005856:Germ-Free Life; D007279:Injections, Subcutaneous; D008095:Lithocholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000009:adverse effects; D051379:Mice; D008813:Mice, Inbred ICR
D001647:Bile Acids and Salts; D002273:Carcinogens; D002793:Cholic Acids; D004127:Dimethylhydrazines; D003840:Deoxycholic Acid; C014202:sulfolithocholic acid; C004821:muricholic acid; D008095:Lithocholic Acid; D008770:Methylnitrosourea; D019813:1,2-Dimethylhydrazine