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Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats
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‐aminosali...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2002
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926955/ https://www.ncbi.nlm.nih.gov/pubmed/11856477 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01252.x |
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author | Narisawa, Tomio Fukaura, Yoko Takeba, Naomi Nakai, Keiko |
author_facet | Narisawa, Tomio Fukaura, Yoko Takeba, Naomi Nakai, Keiko |
author_sort | Narisawa, Tomio |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5926955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59269552018-05-11 Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats Narisawa, Tomio Fukaura, Yoko Takeba, Naomi Nakai, Keiko Jpn J Cancer Res Article 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. Blackwell Publishing Ltd 2002-02 /pmc/articles/PMC5926955/ /pubmed/11856477 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01252.x Text en |
spellingShingle | Article Narisawa, Tomio Fukaura, Yoko Takeba, Naomi Nakai, Keiko Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats |
title | Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats |
title_full | Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats |
title_fullStr | Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats |
title_full_unstemmed | Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats |
title_short | Chemoprevention of N‐Methylnitrosourea‐induced Colon Carcinogenesis by Ursodeoxycholic Acid‐5‐aminosalicylic Acid Conjugate in F344 Rats |
title_sort | chemoprevention of n‐methylnitrosourea‐induced colon carcinogenesis by ursodeoxycholic acid‐5‐aminosalicylic acid conjugate in f344 rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926955/ https://www.ncbi.nlm.nih.gov/pubmed/11856477 http://dx.doi.org/10.1111/j.1349-7006.2002.tb01252.x |
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