Lewis J G, Odom B, Adams D O
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Toxicol Appl Pharmacol. 1988 Feb;92(2):246-54. doi: 10.1016/0041-008x(88)90384-5.
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 H2O2 release 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 histocompatibility 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.
苯对动物和人类而言是一种强效骨髓毒素。动物研究表明，接触苯会改变T淋巴细胞功能，并降低动物对单核细胞增生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。本文所呈现研究的目的是确定苯及其代谢产物对巨噬细胞功能以及巨噬细胞被激活以发挥宿主防御中重要功能的能力的影响。苯对所测试的任何巨噬细胞功能或激活均无影响。相反，苯的代谢产物邻苯二酚（CAT）、对苯二酚（HQ）、苯醌（BQ）和1,2,4 -苯三酚（BT）对巨噬细胞功能和激活具有强大且多样的影响。BQ抑制的功能范围最广，包括过氧化氢（H2O2）释放、Fc受体介导的吞噬作用、干扰素γ引发的肿瘤细胞溶解以及细菌脂多糖（LPS）引发的细胞溶解。BQ也是在较低浓度下比其他代谢产物更具抑制作用的代谢产物。HQ抑制H2O2释放和细胞溶解引发，BT抑制吞噬作用和细胞溶解引发。CAT仅抑制H2O2释放。所测试的化合物均未抑制细胞表面II类组织相容性抗原的诱导。所有测量的效应都是在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下发生的。综合这些数据表明，苯代谢产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。
