TOXIC EFFECTS OF BENZOPYRENE ON IMMUNOCOMPETENT CELLS

拟议的研究涉及毒性作用的基本机制

The proposed research deals with the basic mechanisms of the toxic effects of Benzopyrenes on the immune system. It has been previously demonstrated that the polycyclic aromatic hydrocarbons (PAHs) exert suppressive effects upon immunocompetence as well as being potent carcinogens. Previous studies have relied on mixed populations of cells to define the toxicologic actions of PAHs, and Benzopyrenes in particular, on immuno competent cells. It is the goal of this research to delineate the suppressive effect of benzo(a)pyrene using purified populations of cells and defined functional assays and to identify the ultimate macromolecular targets of benzopyrene-induced effects. Once the target cell(s) are identified, the mechanism(s) of alteration will be investigated. Studies are designed to determine if T or B lymphocyte populations and subpopulations are compromised in number, expression of cell surface antigens, ability to produce and respond to soluble mediators, to repond to antigens and to regulate cellular interactions. Studies are also designed to identify differences in Benzopyrene-DNA adduct formation in affected target cell populations versus unaffected populations. Macromolecular synthesis and expression of cell surface proteins will be examined in identified target cell populations from Benzo(a)pyrene-exposed and normal animals. The immunomodulatory effects of the carcinogenic benzopyrenes will be compared to the effects of selected noncarcinogenic congeners. These studies should allow us to rigorously define the target cells and basic mechanisms of benzopyrene immunomodulation. In addition, the effects of the carcinogenic and noncarcinogenic benzopyrenes can be related to differences in their mode of action on immunocompetent cells. This information should contribute to our knowledge of cellular regulation in the immune system. Furthermore, these studies will begin to relate structure of the benzopyrenes to their immunomodulating activity in defined populations of cells.