Toxic effects of benzene and benzene metabolites on mononuclear phagocytes.
Toxic effects of benzene and benzene metabolites on mononuclear phagocytes.
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苯和苯代谢物对单核吞噬细胞的毒性作用。
DOI：
10.1016/0041-008x(88)90384-5
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发表时间：
1988
影响因子：
3.8
通讯作者：
Adams,DO
中科院分区：
文献类型：
--
作者：
Lewis,JG;Odom,B;Adams,DO
苯对动物和人类来说是一种强效骨髓毒素。动物研究表明，接触苯可以改变 T 淋巴细胞功能，降低动物对单核细胞增多性李斯特菌和移植肿瘤细胞的抵抗力。单核吞噬细胞参与宿主对李斯特菌和肿瘤细胞的抵抗。这里提出的研究的目的是确定苯和苯代谢物对巨噬细胞功能的影响以及巨噬细胞被激活以发挥宿主防御中重要功能的能力。苯对巨噬细胞功能或任何测试功能的激活没有影响。相反，苯、儿茶酚 (CAT)、氢醌 (HQ)、苯醌 (BQ) 和 1,2,4-苯三醇 (BT) 的代谢物对巨噬细胞功能和激活具有强大且多样的影响。 BQ 抑制最广泛的功能，包括 H2O2 的释放、Fc 受体介导的吞噬作用、肿瘤细胞溶解的干扰素 γ 启动以及细菌脂多糖 (LPS) 引发的细胞溶解。 BQ 也是最有效的代谢物，与其他代谢物相比，在较低浓度下即可产生抑制作用。 HQ 抑制 H2O2 释放并引发细胞溶解，BT 抑制吞噬作用并引发细胞溶解。 CAT仅抑制H2O2的释放。所测试的化合物均不抑制细胞表面上II类组织相容性抗原的诱导。所有测量的效果均使用不破坏细胞完整性或抑制蛋白质合成等一般功能的化合物浓度进行。综上所述，这些数据表明苯代谢物通过多种机制改变巨噬细胞功能，包括抑制输出酶和破坏信号转导系统。
Benzene is a potent bone marrow toxin in animals and man. Animal studies have shown that exposure to benzene can alter T lymphocyte functions and decrease the resistance of animals to Listeria monocytogenes and transplanted tumor cells. Mononuclear phagocytes participate in host resistance to Listeria and tumor cells. The purpose of the studies presented here was to determine the effects of benzene and benzene metabolites on macrophage functions and the ability of macrophages to be activated for functions which are important in host defense. Benzene had no effects on macrophage function or activation for any of the functions tested. Conversely, metabolites of benzene, catechol (CAT), hydroquinone (HQ), benzquinone (BQ), and 1,2,4-benzenetriol (BT) had potent and varied effects on macrophage function and activation. BQ inhibited the broadest range of functions including release of H2O2, Fc receptor-mediated phagocytosis, interferon gamma priming for tumor cell cytolysis, and bacterial lipopolysaccharide (LPS) triggering of cytolysis. BQ was also the most potent metabolite causing inhibition at lower concentrations than the other metabolites. HQ inhibited H2O2release and priming for cytolysis and BT inhibited phagocytosis and priming for cytolysis. CAT only inhibited the release of H2O2. None of the compounds tested inhibited the induction of class II histocompatability antigens on the cell surface. All of the effects measured occurred using concentrations of compounds which did not disrupt the cell integrity or inhibit general functions such as protein synthesis. Taken together these data suggest that benzene metabolites alter macrophage function through several mechanisms including inhibition of output enzymes and disruption of signal transduction systems.