Mutagenicity testing of a commercial extract from Rutae Herba (Tinctura Rutae) revealed a strong effect in Salmonella typhimurium strain TA98 without S9 mix. In the presence of S9 mix only a weak response was observed. Moderate mutagenic effects were detected with and without S9 mix using strain TA100. The extract used contained the furoquinoline alkaloids dictamnine, gamma-fagarine, skimmianine, pteleine and kokusaginine, as indicated by g.c. and g.c.-m.s. analysis. The pure compounds exhibited a mutagenic activity only in the presence of S9 mix in strain TA98 as well as in strain TA100, but their specific mutagenicity differed greatly in strain TA98. We conclude that the extract studied contains different mutagenic activities and that these are only partially due to the furoquinolines present in the extract.
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.
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