It is the long-range plan of this project to evaluate the relationship between the """"""""biologically-effective dose"""""""" for a particular chemical and the effects of prolonged or acute exposure on cellular processes that may be important in tumorigenesis. Animal models and defined human populations exposed to environmental substances will be used to evaluate the quantitative relationship between exposure dose and DNA-adduct levels; to determine the utility of lymphocytes as a molecular dosimeter of environmental exposure; to identify biochemical, molecular and cytogenetic markers to distinguish chemically-exposed individuals from nonexposed; and to evaluate the role of genetic factors in modulating cellular processes that influence the effect of a given exposure. Currently, a procedure has been developed that distinguishes smokers from nonsmokers, and methods are being developed to quantitate DNA adducts in exposed individuals by post-labeling. Individuals have been identified that have been exposed to substances of interest and biochemical assays are developed to determine the relationship of adducts and exposure to cellular processes related to DNA damage and repair. The goals of these studies are to understand some of the basic biochemical systems important to genetic damage in human populations and to apply the knowledge obtained to identify individuals that may be at increased risk to develop cancer in later life.
