Limits...
Functional toxicogenomics: mechanism-centered toxicology.

North M, Vulpe CD - Int J Mol Sci (2010)

Bottom Line: Traditional toxicity testing using animal models is slow, low capacity, expensive and assesses a limited number of endpoints.Functional toxicogenomics, the global study of the biological function of genes on the modulation of the toxic effect of a compound, can play an important role in identifying the essential cellular components and pathways involved in toxicity response.The combination of the identification of fundamental toxicity pathways and mechanism-centered targeted assays represents an integrated approach to advance molecular toxicology to meet the challenges of toxicity testing in the 21(st) century.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Science and Toxicology, University of California Berkeley, Berkeley, California 94720, USA; E-Mail: mnorth@berkeley.edu.

ABSTRACT
Traditional toxicity testing using animal models is slow, low capacity, expensive and assesses a limited number of endpoints. Such approaches are inadequate to deal with the increasingly large number of compounds found in the environment for which there are no toxicity data. Mechanism-centered high-throughput testing represents an alternative approach to meet this pressing need but is limited by our current understanding of toxicity pathways. Functional toxicogenomics, the global study of the biological function of genes on the modulation of the toxic effect of a compound, can play an important role in identifying the essential cellular components and pathways involved in toxicity response. The combination of the identification of fundamental toxicity pathways and mechanism-centered targeted assays represents an integrated approach to advance molecular toxicology to meet the challenges of toxicity testing in the 21(st) century.

Show MeSH

Related in: MedlinePlus

Schematic representation of parallel deletion analysis (PDA). PDA quantifies the relative abundance of each deletion strain in the pool. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Genetics [28], copyright 2001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC3100848&req=5

f1-ijms-11-04796: Schematic representation of parallel deletion analysis (PDA). PDA quantifies the relative abundance of each deletion strain in the pool. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Genetics [28], copyright 2001.

Mentions: Functional toxicogenomics is functional genomics in the context of toxicology, i.e., the study of the requirement for the biological activities of genes and proteins in the response of, and effect on, an organism by a toxicant [12]. In the budding yeast Saccharomyces cerevisiae, global (genome-wide) analysis of gene function was initially attempted using different applications of random mutagenesis to abolish gene function [25–27]. The sequencing of S. cerevisiae, the first eukaryote genome to be sequenced, allowed a directed all-inclusive approach to be taken. All identified genes were systematically deleted through a PCR-based approach, using unique 20 bp “barcodes” to disrupt ORFs and creating a set of “knockout” yeast strains for both non-essential and essential genes. An important consequence of “molecular barcoding” is that multiple deletion strains can be pooled and assayed for growth simultaneously (Figure 1).


Functional toxicogenomics: mechanism-centered toxicology.

North M, Vulpe CD - Int J Mol Sci (2010)

Schematic representation of parallel deletion analysis (PDA). PDA quantifies the relative abundance of each deletion strain in the pool. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Genetics [28], copyright 2001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100848&req=5

f1-ijms-11-04796: Schematic representation of parallel deletion analysis (PDA). PDA quantifies the relative abundance of each deletion strain in the pool. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Genetics [28], copyright 2001.
Mentions: Functional toxicogenomics is functional genomics in the context of toxicology, i.e., the study of the requirement for the biological activities of genes and proteins in the response of, and effect on, an organism by a toxicant [12]. In the budding yeast Saccharomyces cerevisiae, global (genome-wide) analysis of gene function was initially attempted using different applications of random mutagenesis to abolish gene function [25–27]. The sequencing of S. cerevisiae, the first eukaryote genome to be sequenced, allowed a directed all-inclusive approach to be taken. All identified genes were systematically deleted through a PCR-based approach, using unique 20 bp “barcodes” to disrupt ORFs and creating a set of “knockout” yeast strains for both non-essential and essential genes. An important consequence of “molecular barcoding” is that multiple deletion strains can be pooled and assayed for growth simultaneously (Figure 1).

Bottom Line: Traditional toxicity testing using animal models is slow, low capacity, expensive and assesses a limited number of endpoints.Functional toxicogenomics, the global study of the biological function of genes on the modulation of the toxic effect of a compound, can play an important role in identifying the essential cellular components and pathways involved in toxicity response.The combination of the identification of fundamental toxicity pathways and mechanism-centered targeted assays represents an integrated approach to advance molecular toxicology to meet the challenges of toxicity testing in the 21(st) century.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Science and Toxicology, University of California Berkeley, Berkeley, California 94720, USA; E-Mail: mnorth@berkeley.edu.

ABSTRACT
Traditional toxicity testing using animal models is slow, low capacity, expensive and assesses a limited number of endpoints. Such approaches are inadequate to deal with the increasingly large number of compounds found in the environment for which there are no toxicity data. Mechanism-centered high-throughput testing represents an alternative approach to meet this pressing need but is limited by our current understanding of toxicity pathways. Functional toxicogenomics, the global study of the biological function of genes on the modulation of the toxic effect of a compound, can play an important role in identifying the essential cellular components and pathways involved in toxicity response. The combination of the identification of fundamental toxicity pathways and mechanism-centered targeted assays represents an integrated approach to advance molecular toxicology to meet the challenges of toxicity testing in the 21(st) century.

Show MeSH
Related in: MedlinePlus