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Effects of Oral Administration of Sulfolithocholic Acid Disodium Salt and Lithocholic Acid Sodium Salt on N-Methyl-N-nitrosourea-induced Colonic Tumorigenesis in Conventional Rats

Department of Internal Medicine 4, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663 [N. T., K. S., A. K., M. O., T. S.], and Department of Surgery, Akita University School of Medicine, 1-1 Hondo 1-chome, Akita 010 [T. N.], Japan

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.

¹ To whom requests for reprints should be addressed.

Received 6/13/88. Revised 10/17/88. Accepted 11/22/88.