Sebestová L, Seifert J, Jiricka Z, Kolar G F
Institute of Pharmacology, Academy of Sciences of the Czech Republic, Prague.
Toxicology. 1994 Sep 6;92(1-3):27-38. doi: 10.1016/0300-483x(94)90165-1.
Three isomers of trifluoromethylaniline (TFMA) were investigated for their possible different toxic effects on the hematopoietic system in male Wistar rats. The effects of isomeric 2-, 3- and 4-TFMA were compared with those of aniline, the prototypic drug. Strong leukocytosis manifested by considerable increase in the number of all respective white blood elements was observed in the peripheral blood 1 day after the administration of 4-TFMA. In contrast, erythropoiesis, as ascertained by erythrocyte count and hemoglobin concentration, was inhibited by 4-TFMA. The determination of the ED50 revealed lymphocytes to be the most responsive elements towards 4-TFMA administration. Besides hyperemic and proliferative splenomegaly the histological changes in maturation of immunocompetent cells following the 4-TFMA administration were found also in thymus. In accord with an enhanced incorporation of [3H]thymidine, the specific activity of thymidine kinase (TdK) in spleen was increased after a single dose of 4-TFMA. Activities of the catabolic enzymes adenosine deaminase (ADA) and inosine phosphorylase (IP) decreased in both organs with the exception of IP activity in thymus. The effects evoked by the 3-TFMA isomer were regularly less pronounced, and 2-TFMA was nearly inactive.
研究了三氟甲基苯胺（TFMA）的三种异构体对雄性Wistar大鼠造血系统可能存在的不同毒性作用。将异构体2-TFMA、3-TFMA和4-TFMA的作用与原型药物苯胺的作用进行了比较。在给予4-TFMA 1天后，外周血中观察到明显的白细胞增多，表现为所有各类白细胞数量显著增加。相比之下，通过红细胞计数和血红蛋白浓度确定，4-TFMA抑制了红细胞生成。半数有效剂量（ED50）的测定表明，淋巴细胞是对给予4-TFMA反应最敏感的细胞成分。除了充血性和增殖性脾肿大外，在给予4-TFMA后，胸腺中也发现了免疫活性细胞成熟的组织学变化。与[3H]胸腺嘧啶核苷掺入增加一致，单次给予4-TFMA后，脾脏中胸苷激酶（TdK）的比活性增加。除胸腺中的肌苷磷酸化酶（IP）活性外，两种器官中分解代谢酶腺苷脱氨酶（ADA）和肌苷磷酸化酶（IP）的活性均降低。3-TFMA异构体引起的效应通常不太明显，而2-TFMA几乎没有活性。
