MacEachern L, Snyder R, Laskin D L
Joint Graduate Program in Toxicology, Rutgers University, Piscataway, New Jersey 08855-0789.
Toxicol Appl Pharmacol. 1992 Dec;117(2):147-54. doi: 10.1016/0041-008x(92)90231-g.
Benzene is a well-established hematotoxin that affects developing leukocytes and erythrocytes as well as bone marrow stromal cells. In the present studies we analyzed the effects of benzene on the morphology and functional activity of bone marrow phagocytes. Male Balb/c mice were treated with benzene (660 mg/kg) once per day for 3 days. Bone marrow cells were then isolated and fractionated by density gradient centrifugation. Using highly sensitive techniques in flow cytometry/cell sorting, we found that we could separate three distinct populations of bone marrow cells that differed with respect to size and density. Monoclonal antibody binding and cell sorting revealed a large, dense population that consisted predominantly of granulocytes, a smaller, less dense population of lymphocytes, and a population of intermediate size and density consisting of mononuclear phagocytes and precursor cells. Differential staining of sorted mononuclear phagocytes revealed that benzene treatment of mice caused a marked increase in the number of mature, morphologically activated macrophages in the bone marrow. Benzene treatment of mice also resulted in enhanced chemotaxis and production of hydrogen peroxide by bone marrow granulocytes and mononuclear phagocytes. In contrast, treatment of mice with the combination of hydroquinone and phenol (50 mg/kg each, 1 x/day, 3 days), two metabolites of benzene, resulted in a significant (p < or = 0.02) depression of granulocyte chemotaxis and had no effect on hydrogen peroxide production by bone marrow phagocytes compared to cells from control animals. Taken together these results demonstrate that benzene causes increased differentiation and/or activation of phagocytes in the bone marrow.
苯是一种公认的血液毒素，会影响发育中的白细胞、红细胞以及骨髓基质细胞。在本研究中，我们分析了苯对骨髓吞噬细胞形态和功能活性的影响。雄性Balb/c小鼠每天接受一次苯（660毫克/千克）处理，持续3天。然后通过密度梯度离心分离并分级骨髓细胞。使用流式细胞术/细胞分选的高灵敏度技术，我们发现可以分离出三种不同的骨髓细胞群体，它们在大小和密度方面存在差异。单克隆抗体结合和细胞分选显示，一个大的、密度高的群体主要由粒细胞组成，一个较小的、密度较低的群体是淋巴细胞，还有一个中等大小和密度的群体由单核吞噬细胞和前体细胞组成。对分选的单核吞噬细胞进行鉴别染色显示，用苯处理小鼠会导致骨髓中成熟的、形态学上活化的巨噬细胞数量显著增加。用苯处理小鼠还会增强骨髓粒细胞和单核吞噬细胞的趋化性以及过氧化氢的产生。相比之下，用苯的两种代谢产物对苯二酚和苯酚（各50毫克/千克，每天1次，共3天）联合处理小鼠，与对照动物的细胞相比，会导致粒细胞趋化性显著降低（p≤0.02），并且对骨髓吞噬细胞产生过氧化氢没有影响。综合这些结果表明，苯会导致骨髓中吞噬细胞的分化和/或活化增加。
