IMMUNOTOXIC PROPERTIES OF MERCURIC COMPOUNDS

汞蒸气（HgO）和含汞化合物具有极高的毒性 物质.最近的研究指出，牙科汞合金作为一个点源， HgO。这引起了人们的猜测和关注， 汞合金对牙科医生和病人的健康都有影响。 虽然关于汞的实际含量存在一些争议， 从汞合金中释放出来并被吸收到体内， 一致认为有机形式的汞占汞的大部分， 摄入和吸收汞。因此，这一目标 调查是对有机物的影响进行全面的研究， 汞对人体免疫系统的影响，并确定其机制， 这种金属会损害免疫功能。根本 有待检验的假设是，接触汞可能导致 免疫异常直接或间接损害 暴露个体的健康。 本建议的具体目标是：（1）确定是否暴露于 低浓度的无机汞会加剧 有机汞的免疫毒性作用。此外，我们将扩展这些 确定其他形式的有机汞是否具有免疫毒性， 无机汞也改变了这些化学物质的毒性。 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，并确定是否对T细胞的所有影响 反应需要单核细胞。 (2)为了确定汞化合物是否会改变 单核细胞功能，并探讨提高敏感性的基础 单核细胞对汞的毒性作用。我们计划确定 在汞介导的细胞毒性改变中需要单核细胞的基础 T细胞反应性此外，我们将测试假设， 淋巴细胞和单核细胞对有机汞的敏感性差异， 由于其快速生物转化为Hg++，这是一种过氧化氢酶依赖性 反应(3)确定免疫调节的分子基础 有机汞的影响以及确定有机汞相对敏感性的依据 淋巴细胞对有机汞的毒性我们将测试假设， 汞改变淋巴细胞反应性的机制是通过 细胞的GSH和/或巯基状态的改变。 (4)发展一种 研究汞对人体免疫毒性作用的体内模型系统 淋巴样细胞我们将利用SCID鼠标系统来扩展我们在 从体外观察到允许生物转化的体内形式 和“汇”，研究有机汞、氯化汞和 HGO。 总之，这些研究的结果将进一步加深我们对 汞免疫毒性此外，它们将为以下方面提供基础： 了解与使用、滥用和 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.