CENTER ON ENVIRONMENTAL GENETICS

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.