Ignatius A, Tempel K H
Institute of Pharmacology, Toxicology and Pharmacy, Faculty of Veterinary Medicine, University of Munich, Germany.
Anticancer Drugs. 1992 Oct;3(5):499-505. doi: 10.1097/00001813-199210000-00009.
The influence of suramin on O6-alkylguanine-DNA alkyltransferase (AT), DNase I and poly(adenosine diphosphate ribose)polymerase (PADPR) as well as on primary cultures of rat and chick embryo cells was examined by using some short-term tests. AT and DNase I were inhibited by suramin in a dose-dependent manner (DE50 = 65 and 100 micrograms/ml, respectively). PADPR activity was increased over a concentration range of 40-320 micrograms/ml. At concentrations above 40 micrograms/ml suramin decreased scheduled and unscheduled DNA synthesis. At doses of below 20 micrograms/ml the substance slightly stimulated unscheduled DNA synthesis in embryonic cells. Suramin enhanced nucleoid sedimentation and diminished the viscosity of alkaline cell lysates. From the present results it is concluded that suramin, at clinically relevant concentrations, is able to interact with enzyme systems which are critical to important nuclear functions and to interfere--in a cell specific manner--with histones and/or matrix proteins, resulting in greater chromatin compactness.
通过一些短期试验,研究了苏拉明对O6-烷基鸟嘌呤-DNA烷基转移酶(AT)、脱氧核糖核酸酶I(DNase I)和聚(腺苷二磷酸核糖)聚合酶(PADPR)的影响,以及对大鼠和鸡胚细胞原代培养物的影响。苏拉明以剂量依赖的方式抑制AT和DNase I(DE50分别为65和100微克/毫升)。在40-320微克/毫升的浓度范围内,PADPR活性增加。在浓度高于40微克/毫升时,苏拉明降低了定时和不定时的DNA合成。在剂量低于20微克/毫升时,该物质轻微刺激胚胎细胞中的不定时DNA合成。苏拉明增强了核小体沉降,并降低了碱性细胞裂解物的粘度。从目前的结果可以得出结论,在临床相关浓度下,苏拉明能够与对重要核功能至关重要的酶系统相互作用,并以细胞特异性方式干扰组蛋白和/或基质蛋白,导致染色质更加紧密。