Seifert J, Mostecká H, Kolar G F
Institute of Pharmacology, Czech Academy of Sciences, Prague.
Toxicology. 1993 Oct 25;83(1-3):49-59. doi: 10.1016/0300-483x(93)90091-6.
Reactive isomeric 3- and 4-trifluoromethylanilines (3-,4-TFMA), and control aniline itself, induced the following effects on biosynthesis of DNA in the liver, kidney, thymus and spleen of rats: (a) The administration of 4-TFMA initially suppressed the utilization of labeled thymidine for splenic DNA synthesis during the early prereplicative stage. However, with progressing time the incorporation of the labeled marker began to increase and in 30 h its level exceeded the controls by more than 200%. As expected, aniline administration resulted in mild depression of incorporation during the whole period studied. (b) 4-TFMA caused a significant increase of incorporation of labeled thymidine into DNA thymine also in the thymus. After administration of aniline the utilization of labeled thymidine for the synthesis of DNA thymine in thymus was suppressed during the first 16 h. (c) The dose-response curve showed a linear increase of incorporation in the spleen within the dose range between 0.125 and 0.500 mmol/kg of 4-TFMA. (d) It appears that enhanced incorporation of labeled thymidine into splenic and thymic DNA is a phenomenon specific for compounds bearing the CF3 group on the 4-position of the phenyl ring, such as 4-TFMA and 4-TFMPD. On the contrary, the analogous 3-CF3 substituted derivatives had no effect. Increased incorporation of labeled thymidine into spleen and thymus DNA apparently represents an increased DNA synthesis and cellular proliferation in lymphatic organs. The proliferative response was possibly evoked by the preceding hemolysis or by other toxic effects caused by the drug.
反应性异构体3-和4-三氟甲基苯胺（3-、4-TFMA）以及对照物苯胺本身，对大鼠肝脏、肾脏、胸腺和脾脏中DNA的生物合成产生了以下影响：（a）给予4-TFMA最初在复制前期早期抑制了标记胸苷用于脾脏DNA合成的利用率。然而，随着时间的推移，标记物的掺入开始增加，在30小时时其水平超过对照组200%以上。正如预期的那样，在整个研究期间，给予苯胺导致掺入轻度降低。（b）4-TFMA还导致胸腺中标记胸苷掺入DNA胸腺嘧啶的显著增加。给予苯胺后，胸腺中用于DNA胸腺嘧啶合成的标记胸苷的利用率在最初16小时内受到抑制。（c）剂量反应曲线显示，在0.125至0.500 mmol/kg的4-TFMA剂量范围内，脾脏中的掺入呈线性增加。（d）似乎标记胸苷增强掺入脾脏和胸腺DNA是苯环4位带有CF3基团的化合物（如4-TFMA和4-TFMPD）特有的现象。相反，类似的3-CF3取代衍生物没有影响。标记胸苷掺入脾脏和胸腺DNA的增加显然代表淋巴器官中DNA合成和细胞增殖的增加。增殖反应可能是由先前的溶血或药物引起的其他毒性作用诱发的。
