Trifluoromethylanilines--their effect on DNA synthesis and proliferative activity in parenchymal organs of rats

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.