Transcript TOXICOGENOMICS

TOXICOGENOMICS
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Is the study of the
response of a genome
to environmental
stressors and toxicants
(Waters, et al 2003).
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It combines
genomicstranscriptomics,
proteomics,
metabonomics/metabo
lomics, and
bioinformatics with
conventional
toxicology.
TOXICOGENOMICS
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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/Metabo
lomics
• Furthermore,
metabolites are the last
step in the molecular
response to a toxicants.
TOXICOGENOMICS
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Toxicogenomics has three principals goals
(Waters, MD. et al 2004):
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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.
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Understand the relationship between environmental stress and
human disease susceptibility.
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Elucidate the molecular mechanisms of
toxicity
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Identify useful biomarkers of disease and exposure to toxic substances.
TOXICOGENOMICS
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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):
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Create a reference toxicogenomics information.
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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.
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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./
TOXICOGENOMICS
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Limitations:
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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.
TOXICOGENOMICS
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The future of toxicogenomics:
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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.
TOXICOGENOMICS
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References:
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Waters, MD., Fostel, JM. Toxicogenomics and systems
toxicology: aims and prospects. Nature (2004);5:936948.
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/