Burns L A, White K L, McCay J A, Fuchs B A, Stern M, Brown R D, Musgrove D L, Holsapple M P, Luster M I, Bradley S G
Department of Pharmacology, Virginia Commonwealth University, Richmond 23298.
Drug Chem Toxicol. 1994;17(3):359-99. doi: 10.3109/01480549409017864.
The nitrotoluenes are chemicals used in dyes, agricultural products, pharmaceuticals and explosives. In the present studies, the toxicology and immunotoxicity of meta-nitrotoluene (m-nitrotoluene) were evaluated. Mice, exposed to m-nitrotoluene at dose levels of 200, 400 and 600 mg/kg/body weight for 2 weeks by gastric gavage, gained body weight over the treatment period to a slightly greater extent than the control groups. Of the selected organs weighed, the liver and kidney of mice exposed to m-nitrotoluene were increased in weight while the thymus weight was decreased. The liver of mice exposed to m-nitrotoluene, but not ortho-nitrotoluene, showed slight to moderate swelling of the hepatocytes adjacent to the central veins. The hepatocyte swelling appeared to be reversible and there was no evidence of necrosis. The hematology and serum chemistries examined were unaffected by m-nitrotoluene exposure although there were modest decreases in the percentage of polymorphonuclear leukocytes and eosinophils in differential blood counts. Bone marrow cellularity and the number of CFU/M and CFU/GM were unaffected by m-nitrotoluene exposure. m-Nitrotoluene suppressed the IgM response to sRBC and the DHR response to KLH. There was a slight (8%) decrease in the percentage of B lymphocytes in the spleen. The response to the T cell mitogens was suppressed by as much as 39%. Fc-mediated adherence and phagocytosis of chicken erythrocytes and NK cell activity were increased dose dependently in mice exposed to m-nitrotoluene. Several immune parameters were unaffected by exposure to m-nitrotoluene, including the IgG response to sRBC, responses to the B cell mitogen LPS and to allogeneic cells, and serum interferon levels. Resistance to Streptococcus pneumoniae and Plasmodium yoelii were unaffected also. Resistance to the tumor model PYB6 was increased. Exposure of mice to m-nitrotoluene decreased resistance to Listeria monocytogenes. The decreased resistance to L. monocytogenes may be related to an effect on T cells, evidenced by a decrease in T cell numbers and in the DHR.
硝基甲苯是用于染料、农产品、药品和炸药的化学物质。在本研究中，对间硝基甲苯（m - 硝基甲苯）的毒理学和免疫毒性进行了评估。通过灌胃法让小鼠连续2周暴露于剂量为200、400和600毫克/千克体重的m - 硝基甲苯中，在治疗期间小鼠体重增加幅度略大于对照组。在所称取的选定器官中，暴露于m - 硝基甲苯的小鼠肝脏和肾脏重量增加，而胸腺重量减轻。暴露于m - 硝基甲苯而非邻硝基甲苯的小鼠肝脏中，中央静脉附近的肝细胞出现轻微至中度肿胀。肝细胞肿胀似乎是可逆的，且没有坏死迹象。尽管在分类血细胞计数中多形核白细胞和嗜酸性粒细胞的百分比略有下降，但所检测的血液学和血清化学指标不受m - 硝基甲苯暴露的影响。骨髓细胞密度以及CFU/M和CFU/GM的数量不受m - 硝基甲苯暴露的影响。m - 硝基甲苯抑制了对绵羊红细胞（sRBC）的IgM反应以及对钥孔血蓝蛋白（KLH）的迟发型超敏反应（DHR）。脾脏中B淋巴细胞的百分比略有下降（8%）。对T细胞有丝分裂原的反应被抑制高达39%。在暴露于m - 硝基甲苯的小鼠中，鸡红细胞的Fc介导黏附和吞噬作用以及自然杀伤（NK）细胞活性呈剂量依赖性增加。暴露于m - 硝基甲苯对一些免疫参数没有影响，包括对sRBC的IgG反应、对B细胞有丝分裂原脂多糖（LPS）和同种异体细胞的反应以及血清干扰素水平。对肺炎链球菌和约氏疟原虫的抵抗力也未受影响。对肿瘤模型PYB6的抵抗力增强。小鼠暴露于m - 硝基甲苯会降低对单核细胞增生李斯特菌的抵抗力。对单核细胞增生李斯特菌抵抗力的降低可能与对T细胞的影响有关，这表现为T细胞数量和DHR的下降。
