POTENTIAL FOR ENVIRONMENTAL AND THERAPEUTIC AGENTS TO INDUCE IMMUNOTOXICITY

Virginia Commonwealth University, Richmond VA

Investigators

Abstract

The goal of this contract is to provide support of National Toxicology Program (NTP) hazard identification activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. This contract consists of four components, three primarily involved in the testing of environmental chemicals or therapeutics for their ability to induce immunosuppression, hypersensitivity responses and autoimmunity, and a research and development component. During this period we have conducted studies to examine the relative potencies of four brominated dioxins and furans as compared with their chlorinated counterparts. In depth studies continue to examine the underlying mechanisms by which differential and highly life stage specific immune effects occur following exposure to 1,2,5,6 dibenzanthracene. Additional in-depth studies are investigating the use of antigens other than Sheep Red Blood Cells to evaluate the T-dependent antibody response. We have evaluated several compounds for their potential to induce dermal hypersensitivity including: 2-Methoxy-4-nitroaniline, 2-ethylhexyl p-methoxycinnamate, and a newly formulated vehicle for dermal toxicity studies. The in-life phase of a study to examine the potential of the dietary supplement resveratrol to influence the onset and severity of autoimmune disease in a murine model of type 1 diabetes has been completed and the data analysis is ongoing. The research and development efforts in this contract are directed towards the development of new methods in order to obtain more sensitive endpoints for identifying environmental or therapeutic agents with the potential of having adverse effects on the immune system and inlammatory/immune mediated diseases, and studies aimed at elucidating the mechanisms by which chemicals may alter immune function at the cellular and molecular level. Projects associated with this aspect of the contract for this reporting period have focused on validation activities for alternative endpoints used to assess dermal sensitization.