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TOXICOGENOMICS

TOXICOGENOMICS. It combines genomics-transcriptomics, proteomics, metabonomics/metabolomics, and bioinformatics with conventional toxicology. TOXICOGENOMICS. Is the study of the response of a genome to environmental stressors and toxicants (Waters, et al 2003). TOXICOGENOMICS.

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TOXICOGENOMICS

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  1. TOXICOGENOMICS

  2. It combines genomics-transcriptomics, proteomics, metabonomics/metabolomics, and bioinformatics with conventional toxicology. TOXICOGENOMICS • Is the study of the response of a genome to environmental stressors and toxicants (Waters, et al 2003).

  3. TOXICOGENOMICS • Genomics: the study of genes in the aggregate- DNA, the primary transcript and mRNA. • If we assume there is some change in gene expression in response to toxicity, then expression profiling is an extremely powerful tool to a asses a specific response to environmental exposures.

  4. TOXICOGENOMICS • Proteomics: the study of protein products in aggregate-it applies to the translation from the mRNA to the primary protein products, and their maduration and modification to yield active proteins.

  5. TOXICOGENOMICS • Metabonomics/Metabolomics • Furthermore, metabolites are the last step in the molecular response to a toxicants.

  6. TOXICOGENOMICS • Toxicogenomics has three principals goals (Waters, MD. et al 2004): • Understand the relationship between environmental stress and human disease susceptibility. • Identify useful biomarkers of disease and exposure to toxic substances. • Elucidate the molecular mechanisms of toxicity.

  7. Understand the relationship between environmental stress and human disease susceptibility. • Elucidate the molecular mechanisms of toxicity

  8. Identify useful biomarkers of disease and exposure to toxic substances.

  9. TOXICOGENOMICS • NCT (National Center for Toxicogenomics) has created a public database of environmetal effects of toxic substances in biological systems, CEBS. • CEBS had two majors goals (Waters, MD. et al 2003): • Create a reference toxicogenomics information. • Develope a compendia on toxicologically important genes, groups of genes, SNPs, and mutant and knockout phenotypes in animal models relevant to human health and environmental disease.

  10. CEBS has incorporated high-quality data sets from each of new toxicogenomics technologies as well as from contemporary molecular and celular toxicology. http://cebs.niehs.nih.gov./

  11. TOXICOGENOMICS • Limitations: • Difficulty in analysis of high density data. • Difficulty in integration of data obtained by different technologies. • Difficulty in linking “omics” data to specific adverse effects. • Difficulty in translation statistical assessments into biological understanding. • Limitations of incomplete functional annotation of genome data bases. • Incomplete knowledge of functional pathways and networks, particularly trans-genome relationship.

  12. TOXICOGENOMICS • The future of toxicogenomics: • Genomic technologies provides an opportunity to asses the problematic relationship between environmental exposure and disease. • Identify biomarkers of incipient adverse effects, that will be more specific and sensitive than available now. • Provide a rational basis for risk assesment. • Facilitate the identification of specific susceptibility polymorphisms and relate them to environmental diseases. • Facilitate the development on new drugs- impact on pharmaceutical industry. • Keep on improve the CEBS knowledge base, specially in human data.

  13. TOXICOGENOMICS • References: • Waters, MD., Fostel, JM. Toxicogenomics and systems toxicology: aims and prospects. Nature (2004);5:936-948. • Waters, MD., Selrik, JK., Olden, K. The impact of new technologies on human population studies. Mutation Research (2003);544:349-360. • Waters, MD., Olden, K., Tennant, RW. Toxicogenomic approach for assesing toxicant-related disease. Mutation Research (2003);544:415-424. • http://cebs.niehs.nih.gov/

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