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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2002 Feb;93(2):143–150. doi: 10.1111/j.1349-7006.2002.tb01252.x

Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats

Tomio Narisawa 1,✉, Yoko Fukaura 1, Naomi Takeba 2, Keiko Nakai 2
PMCID: PMC5926955  PMID: 11856477

Abstract

Bile acids enhance colon carcinogenesis in animal models, whereas ursodeoxycholic acid (UDCA) suppresses it. Nonsteroid anti‐inflammatory drugs prevent colon cancer development in animals and humans. The aim of the present study was to explore the inhibitory effect of UDCA conjugate with 5‐aminosalicylic acid (5‐ASA), UDCA‐5‐ASA conjugate (UDCA‐5‐ASA), against colon carcinogenesis in rats. One‐hundred‐and‐twenty‐nine 7‐week‐old F344 rats received an intrarectal instillation of 2 mg of N‐methylnitrosourea 3 tunes a week for 3 weeks, and were fed a 0% (control), 0.11% or 0.02% UDCA‐5‐ASA‐, 0.08% UDCA‐ or 0.03% 5‐ASA‐supplemented diet for the next 27 weeks. The test diets contained an equimolar amount of a test agent, 2.0 mmol/kg diet, except for the 0.02% UDCA‐5‐ASA diet. The tumor incidence and the mean number of tumors/rat at week 30 were significantly lower and smaller in the UDCA‐5‐ASA diet groups, 48% and 0.7 in both, and marginally lower in the UDCA and 5‐ASA diet groups, 56% and 0.9, and 64% and 0.8, compared to the control group, 83% and 1.3. All the tumors were polypoid in shape, and most of them were differentiated adenocarcinomas restricted to the mucosa or submucosa. An analysis by HPLC for bile acids and 5‐ASA in the feces and serum collected at week 30 showed that one‐half of ingested UDCA‐5‐ASA was cleaved into UDCA and 5‐ASA in the colon. Thus, the two moieties may have independently affected the promotion stage of carcinogenesis.

Keywords: Colon cancer, Chemoprevention, Ursodeoxycholic acid, Aminosalicylic acid, Ursodeoxycholic acid‐5‐aminosalicylic acid conjugate

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