Defining the molecular and cellular basis of toxicity using comparative models

Area of Science:

• Toxicology
• Comparative Biology
• Genomics

Background:

• The selection of appropriate experimental models is fundamental to scientific inquiry, as emphasized by Bernard and Krogh.
• Historically, nonmammalian or nonclassical models were underutilized for human biology research due to perceived complexity differences.
• Genome sequencing reveals significant genetic similarities between humans and ancient organisms, challenging previous perceptions.

Purpose of the Study:

• To highlight the value of alternative animal models in toxicology research.
• To demonstrate how unique attributes of these models can elucidate the molecular and cellular basis of toxicity.
• To provide examples of specific models and approaches used in various toxicology fields.

Main Methods:

• Review and synthesis of existing scientific principles and findings.
• Identification of special attributes of alternative animal models.
• Presentation of selected examples of animal models and experimental approaches.

Main Results:

• Nonmammalian and nonclassical models possess unique attributes exploitable for toxicity studies.
• These models provide valuable insights into neurotoxicology, reproductive and developmental toxicology, organ systems toxicology, carcinogenesis, and functional genomics/toxicogenomics.
• Models such as fish, avian species, Drosophila, Caenorhabditis elegans, and yeast are highlighted for their utility.

Conclusions:

• The use of alternative animal models is strongly supported by comparative genomics and historical scientific principles.
• These models are essential for defining the molecular and cellular basis of toxicity.
• Further exploitation of these models will advance our understanding of human biology and toxicology.