A symposium entitled, "Genomic Information as a Frontier of Toxicology: Building Bridges in Biology" was presented on March 10, 1997, at the annual meeting of the Society of Toxicology in Cincinnati, Ohio. Four investigators involved in cutting-edge, Genome-related research described their work and its application to the field of toxicology, including J.C. Venter, A.V. Carrano, H.N. Wagner, and R.P. Woychik. The perspective of the Department of Energy (DOE) Health Effects Research Program on the potential role of genome technologies in toxicology was presented by J.R. Beall. Brief summaries of the presentations follow.

J.R. Beall (DOE Health Effects Research Program, Germantown, MD)
DOE is committed to funding research that capitalizes on the information and technologies obtained in the course of the Human Genome Project. Among its potentials, genomics can provide a new avenue to understand toxicological mechanisms at the molecular level, i.e. the relationship between exposure to exogenous substances and changes in gene function, and to engineer better animal models of human diseases.

J.C. Venter (The Institute for Genomic research, Rockville, MD)
Complementary DNA (cDNA) clones representing about 80% of the human genes have been sequenced from various organs and tissues, and used to prepare expressed sequence tags (ESTs) for comparative gene expression studies. Potential applications include the toxicological effects of drugs on gene expression, carcinogenesis, and cell cycle progression.

A.V. Carrano (Lawrence Livermore National Laboratory, Livermore, CA)
The Human Genome Project has led to the discovery and isolation of many genes. We are now at the stage of determining the structure and function of those genes, i.e. Functional Genomics. Genes discovered include those involved in the response to toxic exposure such as DNA repair and xenobiotic metabolism. Homologous genes in other species of animals, especially the mouse, can be used as model systems to determine the function of unknown genes.

H.N. Wagner, Jr. (Johns Hopkins School of Public Health, Baltimore, MD)
Genomics is providing a new approach to conduct medical research and to study the function of genes involved in disease processes. By the measurement of in situ biochemistry using phenotypic markers, gene expression can be translated into phenotypic expression. Examples of genes studied include the multidrug resistance gene MDR1 (p-glycoprotein) and a gene involved in Alzheimer's disease (apolipoprotein E4).

R.P. Woychik (Oak Ridge National Laboratory, Oak Ridge, TN)
Developmental mechanisms, and how they can be affected by toxicants, can be studied by insertional (random) mutagenesis and targeted mutagenesis (homologous recombination). Large sections of mouse genes can be replaced with their human counterparts, or endogenous mouse genes can be inactivated ("knockout" mice) and their effect on development studied. In the mutated animals, both the temporal and spatial expression of the genes can be evaluated.

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