Active natural compounds perturb the melanoma risk-gene network
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ABSTRACT:
PROVIDER: PRJNA1032634 | ENA |
REPOSITORIES: ENA
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Project description:It has been proposed that endogenously formed N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as one of the critical factors in the formation of endogenous NOCs, it is of high importance to replace or reduce the nitrite levels in meat. Therefore, the PHYTOME project was initiated (Phytochemicals to reduce nitrite in meat products; www.phytome.eu), an EU funded research project aiming to develop innovative meat products in which the food additive sodium nitrite (E251) has been replaced by natural compounds originating from fruits and vegetables. A human dietary intervention study was conducted in which healthy subjects consumed 300 grams of meat for two weeks, in subsequent order: normal processed red meat, white meat, and red processed meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of standard-nitrite PHYTOME meat products leads to a significant reduction in Apparent Total N-nitroso Compounds (ATNC) levels in faecal water, a surrogate marker of endogenously formed NOCs, as compared to the consumption of conventional processed red meat products. A reduction of nitrite in the PHYTOME meat lowered these levels even further. In addition, DNA strand breaks induced in ex-vivo faecal water exposed Caco-2 cells and O6-methyl-guanine adducts levels in colonic DNA were significantly higher after consumption of normal processed red meat as compared to white meat intake. PHYTOME meat intake resulted in reduced levels of these genotoxic markers, however, these were not statistically significant. Whole genome gene expression analyses in colonic tissue identified differentially expressed genes and genes associated with ATNC, which are related to molecular pathways which may explain cancer risk initiation after intake of processed red meat and cancer risk prevention after intake of the PHYTOME meat. Together these results indicate that addition of natural extracts to conventional processed red meat products results in reduced endogenous formation of NOCs, and may therefore contribute to a reduced risk of CRC, which is mechanistically supported by gene expression analyses.
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Project description:Study hypothesis: We hypothesise that both colon inflammation and a diet high in red meat increase the endogenous formation of potentially carcinogenic N-nitroso compounds in the human colon and that these compounds increase the colorectal cancer risk, which could (partially) explain the increased colorectal cancer risk that is associated with inflammatory bowel disease and diets high in red meat.
Inflammatory bowel disease is characterised by a chronic inflammation within the gastrointestinal tract, which, in case of ulcerative colitis, is present in the colon and rectum.
Primary outcome(s): 1. Whole genome gene expression modifications by microarray analysis (4x44K Agilent platform)
2. Apparent total nitroso compounds in faecal matter by thermal energy analysis
3. Faecal water genotoxicity (30 minute exposure to 10% faecal water) by comet assay analysis in the adenocarcinoma cell line Caco-2
All outcomes are measured at baseline and post intervention.
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