TOXICOGENOMICS. Is the study of the response of a genome to environmental stressors and toxicants...

TOXICOGENOMICS

TOXICOGENOMICS Is the study of the

response of a genome to environmental stressors and toxicants (Waters, et al 2003).

It combines genomics-transcriptomics, proteomics, metabonomics/metabolomics, and bioinformatics with conventional toxicology.

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.

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.

TOXICOGENOMICS

• Metabonomics/Metabolomics

• Furthermore, metabolites are the last step in the molecular response to a toxicants.

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.

Understand the relationship between environmental stress and human disease susceptibility.

Elucidate the molecular mechanisms of toxicity

Identify useful biomarkers of disease and exposure to toxic substances.

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.

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./

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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.

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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.

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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/