Seifert J, Mostecká H, Machková Z, Berger M R, Kolar G F
Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague.
Toxicology. 1990 Jun;62(3):297-310. doi: 10.1016/0300-483x(90)90053-j.
The administration of the lipophilic 3,7-bis-(4-trifluoromethylphenyl)- 1,5,3,7-dioxadiazocane (TFMPD) to rats induced the following effects on the biosynthesis of DNA in the liver, kidney, thymus and spleen: (a) The utilization of [3H]thymidine for the synthesis of liver DNA thymine was decreased after the administration of a single dose of the drug. The depression of the specific activities of DNA pyrimidines of liver DNA in experimental groups was observed also after an injection of [14C]orotic acid. (b) A decreased incorporation of labeled thymidine had occurred also in the spleen during the prereplicative period. Thereafter the specific activity of DNA thymine was higher than in the control group. (c) The observed mitogenic response in the spleen showed a protracted effect; after the administration of a single dose of the drug the specific activity of DNA thymine as well as the thymidine kinase activity of spleen cytosol have been rising up to the ninth day. The same holds true for DNA thymine of the thymus; the activity of thymidine kinase was not affected. (d) Both the single and repeated doses of TFMPD had no marked effect on the levels of microsomal cytochromes P-450 and b5 in the liver and kidney.
给大鼠施用亲脂性的3,7-双-(4-三氟甲基苯基)-1,5,3,7-二恶二氮杂环辛烷(TFMPD)对肝脏、肾脏、胸腺和脾脏中DNA的生物合成产生了以下影响：(a)单次给药后，[3H]胸腺嘧啶核苷用于合成肝脏DNA胸腺嘧啶的利用率降低。在注射[14C]乳清酸后，实验组肝脏DNA嘧啶的比活性也出现下降。(b)在复制前期，脾脏中标记胸腺嘧啶核苷的掺入也减少。此后，DNA胸腺嘧啶的比活性高于对照组。(c)在脾脏中观察到的促有丝分裂反应显示出持久的效应；单次给药后，DNA胸腺嘧啶的比活性以及脾脏细胞溶质的胸腺嘧啶核苷激酶活性一直上升到第九天。胸腺的DNA胸腺嘧啶也是如此；胸腺嘧啶核苷激酶活性未受影响。(d)TFMPD的单次和重复剂量对肝脏和肾脏中微粒体细胞色素P-450和b5的水平均无明显影响。
