Schimmer O, Kiefer J, Paulini H
Institut für Botanik und Pharmazeutische Biologie, Universität Erlangen-Nürnberg, FRG.
Mutagenesis. 1991 Nov;6(6):501-6. doi: 10.1093/mutage/6.6.501.
Eight furocoumarins differing in their basic structure and substitution pattern (angular, linear, dihydrofuran type) were tested for their ability to reduce the mutagenic potency of dictamnine and rutacridone, two alkaloids present in extracts from Ruta graveolens L. Both compounds need metabolic activation by S9 mix in order to exhibit mutagenicity in Salmonella typhimurium strain TA98. The furocoumarins used in this study did not show any mutagenicity either with or without S9 mix within the dose range tested. However, all the furocoumarins were able to inhibit the mutagenicity induced by dictamnine as well as by rutacridone in a dose-dependent manner. Imperatorin turned out to be the most efficient inhibitor. The inhibitory effect is probably due to the inactivation of the cytochrome P450 enzyme complex which prevents the activation of the promutagens. This is indicative of the desmutagenic character of the furocoumarins. However, there is also some evidence that the reduction of the mutagenicity induced by dictamnine might be caused to a small extent by a mechanism which possibly depends on the competition with furocoumarins for the same sites in the DNA molecule.
测试了八种基本结构和取代模式（角型、线型、二氢呋喃型）不同的呋喃香豆素，以考察它们降低白鲜碱和芸香吖啶酮致突变性的能力，这两种生物碱存在于芸香提取物中。这两种化合物在鼠伤寒沙门氏菌TA98菌株中均需经S9混合物代谢活化才能表现出致突变性。本研究中使用的呋喃香豆素在测试剂量范围内，无论有无S9混合物均未显示出任何致突变性。然而，所有呋喃香豆素均能以剂量依赖的方式抑制白鲜碱和芸香吖啶酮诱导的致突变性。欧前胡素被证明是最有效的抑制剂。这种抑制作用可能是由于细胞色素P450酶复合物失活，从而阻止了前诱变剂的活化。这表明呋喃香豆素具有抗诱变特性。然而，也有一些证据表明，白鲜碱诱导的致突变性降低可能在一定程度上是由一种机制引起的，这种机制可能取决于呋喃香豆素与DNA分子中相同位点的竞争。
