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Molecular characterization of the interaction between perfluoroctanoic acid (PFOA) and the hepatocyte nuclear factor 4alpha (HNF4alpha)
Project
Project code: BfR-LMS-08-1322-464
Contract period: 01.03.2011
- 31.12.2011
Purpose of research: Applied research
Perfluoroctanoic acid (PFOA) is needed for the fabrication of various industrial products. PFOA is chemically and biologically inert; it is a global contaminant of water and soil. Con-taminated foodstuff such as drinking water, fish, eggs and game are the main sources for oral uptake of PFOA by the consumer (experts report by the BfR on PFOS and PFOA in food; Sept. 11th 2008). PFOA is toxicologically well characterized and was recently assessed by the EFSA Scien-tific Panel on Contaminants in the Food chain (Febr. 21st 2008). In this report recommenda-tions were given for further research activities, i. e. on the elucidation of the mode of action of PFOA on the molecular level. It is known that PFOA exerts its hepatotoxic effects via acti-vation of the nuclear receptor PPARalpha, however, these data were obtained from animal experiments and may therefore be less relevant for humans. Our own recent data indicate that PFOA affects the activity of the nuclear receptor HNF4alpha in human liver cells. HNF4alpha is a transcription factor with central functions in embryogenesis, liver develop-ment and cellular energy metabolism. Dysfunction of HNF4alpha is correlated with the de-velopment of diabetes. Aim of this project is to characterize the interaction between PFOA and HNF4alpha on the molecular level. Proof of modulation of HNF4alpha activity by PFOA would be an important result relevant to humans and would therefore substantially contrib-ute to the further risk assessment of PFOA.
Section overview
Subjects
- Agricultural hydrology
- Toxicology
