Session 4: Multi-organ Interaction
Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea
ABSTRACT CONTENT / DETAILS:
This project is the construction of the toxicity prediction model based on multi-organ interaction.
Multi-organ interaction system is consisting of liver, kidney and blood vessel. Major concern is metabolic activation in the primary target organ and consequent damage in the secondary target organ.
Integrated discrete Multiple Organ Culture (IdMOC) system was applied for in vitro model (human primary hepatocytes or HepG2, HK-2, HUVEC) for multi-organ interaction.
At first, transient transfection tools were applied for CYP overexpression in HepG2 and stably co-expressed cell lines for major four CYP enzymes, CYP3A4, CYP1A2, CYP2B6, and CYP2E1 was established.
In vitro co-culture system using the CYP-expressing HepG2 was introduced to evaluate toxicity based on metabolic activation and subsequent cellular interaction.
We are collaborating with highly competitive research groups to achieve following subjects:
1) in vivo validation study for toxicity evaluation based on multi-organ interaction,
2) Development of in vitro cell based assay system for evaluating the chemical toxicity induced by multi-organ interaction,
3) Discovery of biomarkers for multi-organ interaction toxicity by Omics approaches,
4) Integrated analysis of associated toxicities in multiple organ and the construction of predictive model.
This research was supported by a grant (13182MFDS988) from Ministry of Food and Drug Safety in 2014.