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Functional toxicology: tools to advance the future of toxicity testing.

Gaytán BD, Vulpe CD - Front Genet (2014)

Bottom Line: Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines.Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines.Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Science and Toxicology, University of California Berkeley Berkeley, CA, USA.

ABSTRACT
The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds-information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes.

No MeSH data available.


Related in: MedlinePlus

Integration of functional assays across organisms. One can use functional tools across a variety of organisms, depending upon the model under study and the end goal of the investigation. For example, one may start with a screen in yeast, mouse, or human cells and extend the analyses to whole organisms such as zebrafish or rodents. Alternatively, one may start with zebrafish mutants or DT40 avian deletion cells and perform follow-up experimentation in human cells or other whole organisms. The many possibilities can advance the future of toxicity testing.
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Figure 3: Integration of functional assays across organisms. One can use functional tools across a variety of organisms, depending upon the model under study and the end goal of the investigation. For example, one may start with a screen in yeast, mouse, or human cells and extend the analyses to whole organisms such as zebrafish or rodents. Alternatively, one may start with zebrafish mutants or DT40 avian deletion cells and perform follow-up experimentation in human cells or other whole organisms. The many possibilities can advance the future of toxicity testing.

Mentions: Functional toxicological screening methods, i.e., those that identify genetic requirements for chemical tolerance, are powerful, unbiased tools which provide unique mechanistic insights in the field of toxicology. High-throughput screens of chemicals of concern or unknown toxicity will allow toxicologists to formulate hypotheses related to their corresponding mechanisms and pathways of toxicity. Automation and deep parallel sequencing technologies will unquestionably increase the throughput of functional techniques, but extensive computational resources and knowledge will be required to implement screening systems and analyze the resulting data. Integration of functional assays across a variety of organisms can identify conserved modes of toxicity and direct studies most relevant to human health (Figure 3). The field of functional toxicology is primed to assist toxicologists meet the need for enhanced chemical toxicity testing.


Functional toxicology: tools to advance the future of toxicity testing.

Gaytán BD, Vulpe CD - Front Genet (2014)

Integration of functional assays across organisms. One can use functional tools across a variety of organisms, depending upon the model under study and the end goal of the investigation. For example, one may start with a screen in yeast, mouse, or human cells and extend the analyses to whole organisms such as zebrafish or rodents. Alternatively, one may start with zebrafish mutants or DT40 avian deletion cells and perform follow-up experimentation in human cells or other whole organisms. The many possibilities can advance the future of toxicity testing.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017141&req=5

Figure 3: Integration of functional assays across organisms. One can use functional tools across a variety of organisms, depending upon the model under study and the end goal of the investigation. For example, one may start with a screen in yeast, mouse, or human cells and extend the analyses to whole organisms such as zebrafish or rodents. Alternatively, one may start with zebrafish mutants or DT40 avian deletion cells and perform follow-up experimentation in human cells or other whole organisms. The many possibilities can advance the future of toxicity testing.
Mentions: Functional toxicological screening methods, i.e., those that identify genetic requirements for chemical tolerance, are powerful, unbiased tools which provide unique mechanistic insights in the field of toxicology. High-throughput screens of chemicals of concern or unknown toxicity will allow toxicologists to formulate hypotheses related to their corresponding mechanisms and pathways of toxicity. Automation and deep parallel sequencing technologies will unquestionably increase the throughput of functional techniques, but extensive computational resources and knowledge will be required to implement screening systems and analyze the resulting data. Integration of functional assays across a variety of organisms can identify conserved modes of toxicity and direct studies most relevant to human health (Figure 3). The field of functional toxicology is primed to assist toxicologists meet the need for enhanced chemical toxicity testing.

Bottom Line: Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines.Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines.Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Science and Toxicology, University of California Berkeley Berkeley, CA, USA.

ABSTRACT
The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds-information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes.

No MeSH data available.


Related in: MedlinePlus