BENZENE TOXICITY AND THE HEMOPOIETIC MICROENVIRONMENT

动物和人类长期接触苯会引起再生障碍性贫血 在血液和人类中完全没有形成的元素，也会导致 几种形式的急性白血病。的形成要素的形成 血液，即造血，是造血干细胞相互作用的结果 具有骨髓基质的细胞，为 调节血细胞前体细胞的增殖和分化。 苯可能对基质微环境有毒性，但靶细胞和 有毒代谢物的身份尚不清楚。方法现在是 可用于液体培养中的造血学研究，该系统 需要骨髓粘附层的形成，它与 在组成和功能上，体内狭窄的间质。这表示一个 研究苯及其代谢物对人体健康影响的理想体系 间质细胞支持造血的能力。一间这样的牢房， 巨噬细胞是粒细胞/巨噬细胞的主要生物合成来源。 集落刺激活性(CSF-GM)，我们之前已经证明 苯抑制巨噬细胞的大分子合成。 因此，目标是确定是否： O苯中毒的部位是骨髓粘附层。 O粘附层中的靶细胞是巨噬细胞。 毒性是由于苯中毒的巨噬细胞不能 产生粒细胞生成所需的生长因子，如GM-CSF。 苯、对苯二酚和对苯二酚的苯醌代谢物 代表有毒物种。 这些实验应该提供有关苯的目标的信息 毒性和有毒物种，从而为进一步研究奠定了基础 苯引起再生障碍性贫血的机制可能提供 关于苯是如何作为白血病原的洞察力。

Chronic exposure of animals and humans to benzene causes aplastic anemia, a complete absence of the formed elements in blood, and in humans also causes several forms of acute leukemia. The formation of the formed elements of the blood, hemopoiesis, results from an interaction of hemopoietic stem cells with the bone marrow stroma which provides a microenvironment for regulated proliferation and differentiation of the blood cell precursors. Benzene may be toxic to the stromal microenviroment but the target cell and the identity of the toxic metabolite are unknown. Methods are now available for studying hemopoiesis in liquid culture, a system which requires the development of a marrow adherent layer which closely resembles in composition and function, the narrow stroma in vivo. This represents an ideal system for studing the effects of benzene and its metabolites on the ability of the cells of thestroma to support hemopoiesis. One such cell, the macrophage, is a major biosynthetic source of granulacyte/macrophage colony-stimulating activity (CSF-GM) and we have previously shown that macromolecular synthesis in the macrophage is inhibited by benzene. Therefore, the aims are to determine whether: o The site of benzene toxicity is the marrow adherent layer. o The target cell in the adherent layer is the macrophage. o Toxicity results from an inability of the benzene-poisoned macrophage to produce growth factors such as GM-CSF required for granulopoiesis. o The quinone metabolites of benzene, hydroquinone and p-benzoquinone represent the toxic species. These experiments should provide information on the target of benzene toxicity and the toxic species and thus pave the way for futher studies on the mechanisms whereby benzene causes aplastic anemia and may provide an insight as to how benzene acts as a leukemogen.