Influence of (processed) red meat on colon cancer: a new in vitro approach

Meat is a valuable nutrient source. Yet, epidemiological studies have revealed the colon cancer inducing effect of red and processed meat products. Therefore, the Superior Health Council has recommended to restrict red and processed meat consumption. Mechanisms behind this effect are still not fully understood, and especially the impact of the colonic environment on later stages of colon cancer progression is not well explored. In this project, novel cell-culture based approaches will be developed to study the impact of the colonic environment, as simulated by in vitro intestinal meat digestion, on colon cancer initiation and progression. First, organoids will be constructed from crypt cells isolated from human intestinal biopts. These organoids, in parallel with existing intestinal cell lines, will be treated with red/processed meat digest compounds on the long term to study especially colon cancer progression. DNA damage and adduct formation will be studied by microscopy and analytical techniques, and the altered cell phenotype will be characterized using live-cell imaging, molecular techniques and LC-MS/MS-based metabolomics. As an in vivo validation, a selection of altered cells will be injected to nu/nu mice to follow up their tumor forming potential and metastasis. In parallel, these mice will be fed white or red/processed meat diets to study synergistic effects. The results of this research may lead towards healthier meat-based food formulations and recommendations.