IMMUNOTOXIC PROPERTIES OF MERCURIC COMPOUNDS

汞蒸气(HGO)和含汞化合物具有剧毒 物质。最近的研究指出，牙科汞齐是一种点源 HGO。这引发了人们对其影响的猜测和担忧 汞齐对牙科医生和患者的健康都有影响。 虽然关于汞的实际含量存在一些争议 从汞合金中释放并吸收到体内，有普遍的 同意有机形式的汞占大部分 摄取和吸收汞。因此，这样做的目的是 调查是对有机污染物的影响进行全面的研究 汞对人体免疫系统的影响，并通过以下方法确定其机制 这种金属会损害免疫功能。最基本的 有待检验的假设是，接触汞可能会导致 直接或间接损害的免疫异常 受影响个人的健康状况。 这项提案的具体目标是：(1)确定是否暴露于 细胞对低浓度无机汞的依赖会加剧 有机汞的免疫毒性作用。此外，我们还将延长这些 以确定其他形式的有机汞是否具有免疫毒性以及是否 无机汞也会改变这些化学物种的毒性。 在这些研究中，我们将确定甲基汞的相对免疫毒性， 乙基汞和苯基汞，并确定是否所有影响T细胞 反应需要单核细胞。(2)确定汞化合物是否会改变 单核细胞功能及增敏基础的探讨 单核细胞对汞的毒性作用。我们计划确定 单核细胞在汞介导的改变中的要求基础 T细胞反应性。此外，我们还将测试以下假设 淋巴细胞和单核细胞对有机汞敏感性的差异 由于其快速生物转化为汞++，而汞++依赖于过氧化氢酶 反应。(3)明确免疫调节的分子基础 有机汞的影响及其相对灵敏度的依据 淋巴样细胞转化为有机汞。我们将检验这一假设 汞改变淋巴细胞反应的机制是通过 细胞的谷胱甘肽和/或硫醇状态的改变。(4)发展智能家居 研究汞对人体免疫毒性作用的活体模型系统 淋巴样细胞。我们将利用SCID鼠标系统来扩展我们的 允许生物转化的体内形式的体外观察 和“汇”，以研究有机汞、HgCl2和 HGO。 综上所述，这些研究的结果将加深我们对 汞免疫毒性。此外，它们将为 了解与使用、滥用和使用有关的健康影响 处理这些有毒化合物。

Mercury vapor (HgO) and mercury containing compounds are extremely toxic substances. Recent studies point to dental amalgam as a point source of HgO. This has lead to speculation and concern regarding the effect of amalgam on the health of both the dental practitioner and the patient. While there is some dispute concerning the actual amount of mercury released from amalgam and absorbed into the body, there is universal agreement that the organic forms of mercury account for most of the ingested and absorbed mercury. Therefore, the objective of this investigation is to conduct a comprehensive study of the effect of organic mercury on the human immune system and to determine the mechanisms by which the metal compromises immunological function. The fundamental hypothesis to be tested is that exposure to mercury may lead to immunological abnormality that either directly or indirectly compromises the health of the exposed individual. The specific aims of this proposal are: (1) To determine if exposure of cells to low concentrations of inorganic mercury exacerbate the immunotoxic effects of organic mercury. Furthermore, we will extend these to determine if other forms of organic mercury are immunotoxic and if inorganic mercury alters the toxicity of these chemical species as well. In these studies we will determine the relative immunotoxicity of MeHg, ethyl mercury and phenyl mercury and determine if all effects on T-cell responses require monocytes. (2) To determine if mercuric compounds alter monocyte function and to explore the basis for the heightened sensitivity of monocytes to the toxic effects of mercury. We plan to determine the basis for the requirement of monocytes in mercury-mediated alterations in T-cell responsiveness. Also, we will test the hypothesis that the differences in lymphocyte and monocyte sensitivity to organic mercury is due to its rapid bioconversion to Hg++, which is a catalase dependent reaction. (3) To define the molecular basis for the immunomodulatory effects of organic mercury and the basis for the relative sensitivities of lymphoid cells to organic mercury. We will test the hypothesis that the mechanism by which mercury alters lymphocyte responsiveness is via the alteration in GSH and/or thiol status of the cell. (4) To develop an in vivo model system to study the immunotoxic effects of mercury on human lymphoid cells. We will utilize the SCID mouse system to extend our in vitro observations to an in vivo format that allows for biotransformations and "sinks", to study the immunotoxicity of organic mercury, HgCl2 and HGO. Together, the results of these studies will further our understanding of mercury immunotoxicity. Furthermore, they will provide a basis for understanding the health implication associated with the use, abuse and disposal of these noxious compounds.