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.
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.
Tanida
N
N
Department of Internal Medicine, Hyogo College of Medicine, Japan.
Sawada
K
K
Kawaura
A
A
Oda
M
M
Shimoyama
T
T
Narisawa
T
T
D000284:Administration, Oral; D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D005243:Feces / Q000032:analysis; D005260:Female; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D008770:Methylnitrosourea; D051381:Rats; D011916:Rats, Inbred F344
C014202:sulfolithocholic acid; D008095:Lithocholic Acid; D008770:Methylnitrosourea