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Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate
BACKGROUND: Intake of red meat is considered a risk factor for colorectal cancer (CRC) development, and heme, the prosthetic group of myoglobin, has been suggested as a potential cause. One of the proposed molecular mechanisms of heme-induced CRC is based on an increase in the rate of lipid peroxida...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094071/ https://www.ncbi.nlm.nih.gov/pubmed/27806694 http://dx.doi.org/10.1186/s12885-016-2874-0 |
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author | Steppeler, Christina Sødring, Marianne Paulsen, Jan Erik |
author_facet | Steppeler, Christina Sødring, Marianne Paulsen, Jan Erik |
author_sort | Steppeler, Christina |
collection | PubMed |
description | BACKGROUND: Intake of red meat is considered a risk factor for colorectal cancer (CRC) development, and heme, the prosthetic group of myoglobin, has been suggested as a potential cause. One of the proposed molecular mechanisms of heme-induced CRC is based on an increase in the rate of lipid peroxidation catalysed by heme. METHODS: In the present work, the novel A/J Min/+ mouse model for Apc-driven colorectal cancer was used to investigate the effect of dietary heme (0.5 μmol/g), combined with high (40 energy %) or low (10 energy %) dietary fat levels, on intestinal carcinogenesis. At the end of the dietary intervention period (week 3–11), spontaneously developed lesions in the colon (flat aberrant crypt foci (flat ACF) and tumors) and small intestine (tumors) were scored and thiobarbituric reactive substances (TBARS), a biomarker for lipid peroxidation was analysed in feces. RESULTS: Dietary hemin significantly reduced colonic carcinogenesis. The inhibitory effect of hemin was not dependent on the dietary fat level, and no association could be established between colonic carcinogenesis and the lipid oxidation rate measured as fecal TBARS. Small intestinal carcinogenesis was not affected by hemin. Fat tended to stimulate intestinal carcinogenesis. CONCLUSIONS: Contradicting the hypothesis, dietary hemin did inhibit colonic carcinogenesis in the present study. The results indicate that fecal TBARS concentration is not directly related to intestinal lesions and is therefore not a suitable biomarker for CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2874-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5094071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50940712016-11-07 Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate Steppeler, Christina Sødring, Marianne Paulsen, Jan Erik BMC Cancer Research Article BACKGROUND: Intake of red meat is considered a risk factor for colorectal cancer (CRC) development, and heme, the prosthetic group of myoglobin, has been suggested as a potential cause. One of the proposed molecular mechanisms of heme-induced CRC is based on an increase in the rate of lipid peroxidation catalysed by heme. METHODS: In the present work, the novel A/J Min/+ mouse model for Apc-driven colorectal cancer was used to investigate the effect of dietary heme (0.5 μmol/g), combined with high (40 energy %) or low (10 energy %) dietary fat levels, on intestinal carcinogenesis. At the end of the dietary intervention period (week 3–11), spontaneously developed lesions in the colon (flat aberrant crypt foci (flat ACF) and tumors) and small intestine (tumors) were scored and thiobarbituric reactive substances (TBARS), a biomarker for lipid peroxidation was analysed in feces. RESULTS: Dietary hemin significantly reduced colonic carcinogenesis. The inhibitory effect of hemin was not dependent on the dietary fat level, and no association could be established between colonic carcinogenesis and the lipid oxidation rate measured as fecal TBARS. Small intestinal carcinogenesis was not affected by hemin. Fat tended to stimulate intestinal carcinogenesis. CONCLUSIONS: Contradicting the hypothesis, dietary hemin did inhibit colonic carcinogenesis in the present study. The results indicate that fecal TBARS concentration is not directly related to intestinal lesions and is therefore not a suitable biomarker for CRC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2874-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-02 /pmc/articles/PMC5094071/ /pubmed/27806694 http://dx.doi.org/10.1186/s12885-016-2874-0 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Steppeler, Christina Sødring, Marianne Paulsen, Jan Erik Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate |
title | Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate |
title_full | Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate |
title_fullStr | Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate |
title_full_unstemmed | Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate |
title_short | Colorectal Carcinogenesis in the A/J Min/+ Mouse Model is Inhibited by Hemin, Independently of Dietary Fat Content and Fecal Lipid Peroxidation Rate |
title_sort | colorectal carcinogenesis in the a/j min/+ mouse model is inhibited by hemin, independently of dietary fat content and fecal lipid peroxidation rate |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094071/ https://www.ncbi.nlm.nih.gov/pubmed/27806694 http://dx.doi.org/10.1186/s12885-016-2874-0 |
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