Gaugler B J, Neumann H G
Chem Biol Interact. 1979 Mar;24(3):355-72. doi: 10.1016/0009-2797(79)90083-8.
Carcinogenic trans-4-dimethylaminostilbene (trans-DAS) and trans-4-acetylaminostilbene (trans-AAS) as well as inactive cis-DAS and DABB were highly and specifically labeled with tritium and administered orally to female Wistar rats. Covalent binding to liver rRNA and DNA was measured and found to be higher for the carcinogenic compounds. Digests from these nucleic acids were chromatographed on Sephadex LH-20 and 16 different nucleoside adducts were characterised by their retention volumes. Labeled trans-DAS was administered in doses ranging from 0.025--250 mumol/kg. Binding to nucleic acids was directly proportional to the dose at low doses (0.025--2.5 mumol/kg) and less than proportional at higher doses (25--250 mumol/kg). The pattern of nucleoside adducts remained practically constant over the wide range of doses. A pharmacokinetically determined threshold of metabolic activation thus could not be demonstrated for this compound. A modified procedure is described to simultaneously isolate pure liver rRNA and DNA from nonfasted rats in high yields.
致癌性反式-4-二甲基氨基芪（反式-DAS）和反式-4-乙酰氨基芪（反式-AAS）以及无活性的顺式-DAS和DABB用氚进行了高度特异性标记，并经口给予雌性Wistar大鼠。测定了它们与肝脏rRNA和DNA的共价结合，发现致癌化合物的结合更高。这些核酸的消化产物在Sephadex LH-20上进行色谱分析，16种不同的核苷加合物通过其保留体积进行表征。标记的反式-DAS以0.025--250 μmol/kg的剂量给药。在低剂量（0.025--2.5 μmol/kg）时，与核酸的结合与剂量成正比，而在高剂量（25--250 μmol/kg）时则小于正比。在很宽的剂量范围内，核苷加合物的模式基本保持不变。因此，无法证明该化合物存在由药代动力学确定的代谢活化阈值。描述了一种改进的方法，可从非禁食大鼠中同时高产率地分离出纯肝脏rRNA和DNA。
