PT07 Chemical and Biological Analysis of Endocrine Disrupting Compounds
Exhibit Hall
8:00 AM - Tuesday
(PT114) Microarray-based toxicogenomics and search of molecular biomarkers in Medaka fish and Mouse.
Kagami, Y1, Nakamura, H1, 1 Ecogenomics, Inc., Kurume, Fukuoka, Japan
ABSTRACT- Endocrine disruption is not simply considered as a toxicological end point, and it might be more appropriate to consider it as a functional change that may lead to adverse effects. So far, a number of biological assays to monitor the effects of endocrine-disrupting chemicals (EDCs) have been developed and applied in environmental protection and risk assessment acts, that are lead by international organizations such as OECD, WHO, European Commission, etc. However, none of these assays involved in evaluation of the EDCs have yet taken a full advantage of gene expression profiling. As the technology advances and molecular biological techniques have sharpened the gene expression analysis using microarrays, we consider that it is about time to make this technology meaningful and accessible for risk assessment of the EDCs, which affect multi-generations of animals (including humans) and is more functional genomics-oriented than the conventional 'one-generation cause-and-effect' toxicology. In our laboratory, we are currently developing Medaka fish (Oryzias latipes) and house mouse (Mus musculus) cDNA microarrays, which will become powerful and efficient tools for the risk assessment of synthetic and natural EDCs. Our custom-made Medaka cDNA microarray has approximately 400 selected genes, and the mouse cDNA microarray has approximately 1400 selected genes. Such gene selection was based on several keywords, for instance 'steroid hormone-responsive' and 'drug metabolism'. cDNA fragments, used as a target genes on the microarray, were 300-350 bases in nucleotide length, and they were generated with sets of gene-specific primers by PCR, purified, and then immobilized on glass microarray slides. In this poster, a part of our preliminary gene expression profiling and statistically analyzed data will be presented and potential applications will be discussed.
Key words: toxicogenomics, endocrine disruptor, microarray, biomarker