A new Center on Environmental Genetics is proposed by the University of Cincinnati. The focus of this Center will be to investigate the impact of genetic diversity on the response of the individual, or populations, to toxic environmental agents. The Center will include a multidisciplinary approach, from "the molecule to the human," devoted to application of molecular biology and genetics to environmental research. The fundamental strategy of the Center is to understand variation in response to toxic agents due to the underlying interindividual differences in genetic predisposition. Basic research may include everything from microbes and lower eukaryotes to mammals and human material. Center research will take advantage of the usefulness of genetic variants, i.e. genetically different subpopulations, resistant versus sensitive groups, and/or interindividual and intraspecies differences. It is clear that interindividual genetic differences can lead to dramatic dissimilarities in the response to a wide variety of environmental substances. An appreciation of these differences, and an understanding of the underlying mechanisms, are critical in the evaluation of risk of adverse health effects caused by toxic environmental agents. Individual variation often reflects allelic differences in genes encoding proteins involved in critical life functions such as receptors, drug metabolism, ion channels, multidrug resistance glycoprotein pumps, second-messenger pathways, DNA repair, and chelation of metals. The elucidation of these functions that can influence interindividual response to toxic agents, and the evaluation of their genetic diversity in the population, will be the central focus of the Center. The identification of these underlying causes of genetic differences in response to toxic agents is an important key to understanding the basic mechanisms of toxicity and provides the basis for both preventing adverse health effects and exploring opportunities for interventions in the disease process. The four Research Cores of the new Center represent existing strengths and interactions among scientists within the University of Cincinnati Medical Center that are relevant to genetics. The central focus of the Ecogenetics Research Core is the identification and characterization of genetic polymorphisms that affect the metabolism, and therefore the toxicity, of foreign chemicals. The other Research Cores--Reproductive & Developmental Toxicology, Genetic Toxicology, and Oxidative Stress Toxicology--are focused on three specific areas of toxicology of major importance. These Research Cores investigate specific toxic effects of environmental agents with an emphasis on the use of genetic techniques. The role of environmental substances in causing infertility, in utero toxicity, and birth defects is an important public health issue. The impact of environmental agents on the structure of genetic material itself, leading to mutations and cancer, is an area of vital importance. Oxidative stress is an emerging area of importance which may underlie many diverse toxic effects of environmental agents in biological systems. This new Center will be unique among NIEHS Centers and will provide. an important. resource to the environmental research community.