TOXIC EFFECTS OF BENZOPYRENE ON IMMUNOCOMPETENT CELLS

拟议的研究涉及毒性作用的基本机制 对免疫系统的影响 之前已经证明 多环芳烃（PAHs）对植物生长有抑制作用， 免疫活性以及潜在的致癌物质。 先前 研究依赖于细胞的混合群体来定义毒理学 多环芳烃，特别是苯并芘对免疫功能的影响 细胞 本研究的目的是描述抑制作用 苯并（a）芘的使用纯化的细胞群和定义 功能测定，并确定最终的大分子目标， 苯并芘诱导效应 一旦识别出目标细胞， 将研究改变的机制。 研究旨在 确定T或B淋巴细胞群和亚群是否 在数量、细胞表面抗原表达、 产生并应答可溶性介质，应答抗原， 调节细胞相互作用。 研究还旨在确定 受影响靶细胞中苯并芘-DNA加合物形成的差异 人口与未受影响的人口。 大分子合成及 将在鉴定的靶细胞中检查细胞表面蛋白的表达。 来自苯并（a）芘暴露动物和正常动物的细胞群。 的 免疫调节作用的致癌苯并芘将进行比较 对特定非致癌同系物的影响。 这些研究应该使我们能够严格定义靶细胞， 苯并芘免疫调节的基本机制。 此外，影响 的致癌和非致癌苯并芘可能与 它们对免疫活性细胞作用方式的差异。 这 信息应该有助于我们了解细胞调节， 免疫系统. 此外，这些研究将开始涉及 苯并芘的结构对其免疫调节活性的影响 细胞群。

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.