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Molecular Toxicity of conjugated linoleic acid isomers and branched chain fatty acids; The role of the nuclear receptor PPAR in colon carcinogenesis
Project
Project code: BfR-LMS-08-1350-002
Contract period: 01.04.2006
- 31.05.2010
Purpose of research: Applied research
The investigation of potential cellular-toxic characteristics of trans fatty acids (TFAs) on the human colon carcinoma cell line Caco-2 is the major intent in this project. The mechanisms of TFA in development of colorectal carcinoma ought to be analysed by modern cell- and molecular-biological methods. Regulatory biomarkers for TFA treatment in Caco-2 shall be identified by genomic approach. The used TFAs vary in chain length and number of double bonds. So it is possible to determine structure-activity-relation. Fatty acids can activate peroxisome proliferator-activated receptors (PPARs). PPARs are ligand induced transcription factors. There are three isoforms, which vary in tissue expression and function. In the intestine all three isoforms are expressed, but we only focus on isoform PPARdelta because recent studies confirm the assumption that there is a correlation between PPARdelta and the accruement of colon carcinoma. Now our point of interest is the potential interaction of the used TFAs and PPARdelta. Can they also activate this transcription factor and so cause to an increased incidence of colon polyps and ? tumours? To answer this question following parameters shall be investigated:proliferation (characterized through measurement of cell rate and expression of the genesc-myc, c-jun and cyclin-D),differentiation (characterized through expression of the alkaline phosphatase and saccharase-isomaltase),cell adhesion (characterized through ß-catenin, E-cadherin und N-CAM) andapoptosis (characterized through FACS analysis with FITC-annexin-V, activity of caspases, DNA-fragmentation and expression of apoptose marker genes).
Section overview
Subjects
- Toxicology
