Project Summary (2006-2009)

Research from various laboratories, including those of Superfund investigators, has established that human populations possess polymorphisms for many enzymes of toxicological relevance. For many, but certainly not all of these polymorphisms, genetic correlates have been identified, and in several molecular epidemiologic investigations, associations have been described between particular polymorphisms in biotransformation genes and the incidence of disease. Biological monitoring increasingly involves assessment of genetic/molecular indices from individuals, for the purpose of detecting possible markers of disease susceptibility, as well as identification of early indicators of chemical effect - such as alterations in gene expression profiles due to exposure to environmental toxicants. Advances in technology supporting molecular research have led to the development of complex techniques which are applicable to a broad range of experimental problems. These and other compelling findings regarding the impact of genetic polymorphisms within biotransformation genes and other gene loci, and their respective involvement in chemically-initiated disease states, form the basis of the long term objective of the Superfund Bioanalytical Core Laboratory - to provide a service facility for Superfund investigators enabling novel genetic assay development, high throughput genetic analysis, and correlates to environmentally-related disease incidence. Eight individual Superfund projects utilize the Bioanalytical Core and benefit from the centralized services. These Core efforts focus on a side range of molecular biology-type biomarkers that may be predictive of exposure to toxicants; impaired physiologic function; and/or unusual susceptibility to damage from toxic agents that occur in the environment, particularly those that are commonly present at hazardous waste sites. Specifically, the Core provides the following services: DNA/RNA extraction, isolation of mononuclear cell samples, development of genotyping assays, creation of new gene expression assays, production of novel DNA sequencing-based assays, identification of genotypes, gene expression analyses, analyses of DNA sequences, and provision of DNA-sequencing gels and gel lanes.