sulfolithocholic-acid and Colonic-Neoplasms

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.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Adenoma; Administration, Oral; Administration, Rectal; Animals; Bile Acids and Salts; Carcinogens; Carcinoma, Squamous Cell; Cholic Acids; Colon; Colonic Neoplasms; Deoxycholic Acid; Dimethylhydrazines; Feces; Female; Germ-Free Life; Injections, Subcutaneous; Lithocholic Acid; Methylnitrosourea; Mice; Mice, Inbred ICR

Effects of p.o. administration of sulfolithocholic acid disodium salt (SLCNa) and lithocholic acid sodium salt (LCNa) on N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis were studied in conventional rats. Female F344 rats received either 0.5 ml of distilled water (DW) alone or DW containing 2.5 mg of MNU twice in 1 wk intrarectally. Then rats were fed freely on a basal diet (PCE-2) or PCE-2 containing LCNa or SLCNa (both at 0.5 mmol/100 g of PCE-2) for 40 wk. Thus, 6 groups were completed: MNU + PCE-2 (n = 30); MNU + LCNa (n = 29); MNU + SLCNa (n = 22); DW + PCE-2 (n = 17); DW + LCNa (n = 20); and DW + SLCNa (n = 19). Numbers of rats bearing colonic tumor were 3 (10%) in MNU + PCE-2, 2 (7%) in MNU + LCNa, and 8 (36%) in MNU + SLCNa group (uncorrected x2 = 9.35 among the 3 groups), but none in those groups without MNU. Total fecal bile acids in the rats given bile salts showed about 2-fold increase compared with those without bile salts. Fecal bile acid profiles between the LCNa and SLCNa groups were indistinguishable except for a slight increase of sulfolithocholic acid in the SLCNa groups. These results indicated that p.o. administration of SLCNa but not LCNa promoted MNU-induced colonic tumorigenesis in conventional rats. Fecal bile acid profiles did not support the higher tumor incidence in the MNU + SLCNa group compared with the MNU + LCNa group, which suggested that an unrecognized mechanism probably relating to desulfation of SLCNa was involved in this phenomenon.

Topics: Administration, Oral; Animals; Colonic Neoplasms; Feces; Female; Lithocholic Acid; Methylnitrosourea; Rats; Rats, Inbred F344