Burns L A, Bradley S G, White K L, McCay J A, Fuchs B A, Stern M, Brown R D, Musgrove D L, Holsapple M P, Luster M I
Department of Pharmacology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Drug Chem Toxicol. 1994;17(3):271-315. doi: 10.3109/01480549409017862.
Nitrobenzene (NBZ) is primarily employed as an oxidizing agent in the synthesis of analine and benzene compounds. It produces myelotoxic effects and effects on erythrocytes in both animal models and man. Reported hepatosplenomegaly and effects on the bone marrow are indicators that NBZ may be immunotoxic. In these studies, female B6C3F1 mice were exposed to 30, 100 and 300 mg/kg of NBZ in corn oil by gavage for 14 consecutive days. To assess the immunotoxic potential of NBZ, body and organ weights were determined and selected immunologic and host resistance responses were studied. In these studies, the liver and spleen appeared to be the primary target organs. Both liver and spleen weights were dose dependently increased. Gross histopathologic examinations revealed significant changes in the spleen, consisting of severe congestion of the red pulp areas with erythrocytes and reticulocytes. Serum chemistry profiles showed increases in alanine aminotransferase and aspartate aminotransferase activities, indicating liver toxicity. Hematologic studies showed a decrease in erythrocyte number and a concomitant increase in mean corpuscular hemoglobin and mean corpuscular volume. A dose-dependent increase in peripheral reticulocytes was also seen. DNA synthesis was enhanced, as was the number of formed elements and the number of monocyte/granulocyte stem cells in the bone marrow of treated mice. IgM responses were decreased and the phagocytic activity of macrophages in the liver was dose dependently increased with a concomitant decrease in the activities in the spleen and lung. Other immunological parameters examined were unchanged. Host resistance to microbial or viral infection was not markedly altered by NBZ; however, there were trends towards increased susceptibility where T-cell function contributes to host defense. These data indicate that NBZ-induced hemolysis and liver injury are linked to the observed alterations in bone marrow activity.
硝基苯（NBZ）主要用作合成苯胺和苯化合物的氧化剂。它在动物模型和人体中都会产生骨髓毒性作用以及对红细胞的影响。报道的肝脾肿大和对骨髓的影响表明NBZ可能具有免疫毒性。在这些研究中，雌性B6C3F1小鼠连续14天经口灌胃给予玉米油中30、100和300mg/kg的NBZ。为了评估NBZ的免疫毒性潜力，测定了体重和器官重量，并研究了选定的免疫和宿主抗性反应。在这些研究中，肝脏和脾脏似乎是主要靶器官。肝脏和脾脏重量均呈剂量依赖性增加。大体组织病理学检查显示脾脏有显著变化，包括红髓区严重充血，有红细胞和网织红细胞。血清化学分析显示丙氨酸转氨酶和天冬氨酸转氨酶活性增加，表明肝脏毒性。血液学研究显示红细胞数量减少，同时平均红细胞血红蛋白和平均红细胞体积增加。外周网织红细胞也呈剂量依赖性增加。DNA合成增强，处理小鼠骨髓中形成的细胞成分数量和单核细胞/粒细胞干细胞数量也增加。IgM反应降低，肝脏中巨噬细胞的吞噬活性呈剂量依赖性增加，同时脾脏和肺中的活性降低。检查的其他免疫参数未改变。NBZ对宿主抵抗微生物或病毒感染没有明显改变；然而，在T细胞功能有助于宿主防御的情况下，有易感性增加的趋势。这些数据表明，NBZ诱导的溶血和肝损伤与观察到的骨髓活性改变有关。
