TOXIC EFFECTS OF BENZOPYRENE ON IMMUNOCOMPETENT CELLS

拟议的研究涉及毒物影响的基本机制。 对免疫系统的影响。它之前已经被证明过 多环芳烃(PAHs)具有抑制作用 对免疫活性的影响，也是强致癌物质。上一首 研究依赖于混合细胞群体来定义毒理学 多环芳烃，特别是苯并吡喃对免疫活性的作用 细胞。描述其抑制作用是本研究的目的。 使用纯化的细胞群体和定义的 功能分析，并确定最终的大分子靶标 苯并(A)芘诱导的效应。一旦识别出目标单元格(S)， 并对其蚀变机理(S)进行探讨。研究的目的是 确定T或B淋巴细胞群体和亚群是否 在数量、细胞表面抗原的表达、 产生并对可溶性介质作出反应，对抗原和 调节细胞间的相互作用。研究的目的也是为了确定 在受影响的靶细胞中苯并[2]-DNA加合物形成的差异 人口与未受影响的人口。大分子合成与研究 细胞表面蛋白的表达将在已确定的目标中进行检测 苯并(A)芘暴露动物和正常动物的细胞群。这个 将比较致癌的苯并吡喃的免疫调节作用。 对选定的非致癌同系物的影响。 这些研究应该允许我们严格定义目标细胞和 苯并(A)芘免疫调节的基本机制。此外，它的影响 致癌的和非致癌的苯并吡喃可以与 它们对免疫活性细胞的作用方式不同。这 信息应该有助于我们对细胞调控的了解 免疫系统。此外，这些研究将开始与 苯并吡喃类化合物的结构对其免疫调节活性的影响 大量的细胞。

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.