An evaluation of 55 commercial plant extracts in the Ames mutagenicity test.

55 commercial phytopharmaceuticals (extracts and tinctures) from 44 plant species were evaluated for mutagenic potential in the Salmonella/mammalian microsome mutagenicity test (Ames assay), utilizing tester strains TA98 and TA100 of Salmonella typhimurium with and without S9 mix from induced rat liver microsomes. Weak activities were detected after exposure of the bacteria to Alchemillae tinctura, Centaurii extractum, Hippocastani extractum and Myrtilli extractum. Moderate effects were observed with Crataegi extractum, Echinaceae angustifoliae extractum, Hyperici tinctura, Rutae tinctura and Trifolii fibrini extractum and tinctura. Quercetin was detected by TLC in all extracts with mutagenic activity except in Echinaceae angustifoliae and Centaurii extractum. From this study and earlier results we suggest that quercetin is possibly the main mutagenic principle in the following phytopharmaceuticals: Alchemillae tinctura, Cratagei extractum, Hippocastani extractum, Hyperici tinctura, Myrtilli extractum, Trifolii fibrini extractum and Trifolii fibrini tinctura.

Inhibitory effects of furocoumarins in Salmonella typhimurium TA98 on the mutagenicity of dictamnine and rutacridone, promutagens from Ruta graveolens L.

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.

Isogravacridonchlorine: a potent and direct acting frameshift mutagen from the roots of Ruta graveolens.

The furanoacridone alkaloid isogravacridonchlorine has been isolated from the roots of Ruta graveolens, the structure was elucidated by spectroscopic means. Its mutagenic activity and mode of action was characterized without as well as with metabolic activation using different Salmonella typhimurium strains.

Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines.

Pentamidine, DAPI and some related compounds (DAI, 6-Br-AI, DPTN, DIPI, 3-Am-DAI, DiaPBF) were investigated in 2 different screening test systems for their potential mutagenic and cytotoxic effects, in the light of their binding to DNA. In the Ames test using Salmonella typhimurium strains TA98 and TA100 with and without metabolic activation no mutagenic effects could be observed. All diamidines tested, except DAI, were toxic at concentrations of 0.5 and 1.0 mumole/plate. In the sister-chromatid exchange (SCE) assay with human peripheral lymphocytes all compounds tested were growth-retarding particularly in the G0 phase. A significant induction of SCEs could only be seen after treatment with the monoamidino compound 6-Br-AI at a concentration of 100 mumole/l. It is concluded from the data obtained that pentamidine and related diamidines in the 2 assays tested show no mutagenic or genotoxic effects, in spite of their tight binding to DNA.

Mutagenicity testing of rutacridone epoxide and rutacridone, alkaloids in Ruta graveolens L., using the Salmonella/microsome assay.

The mutagenicity of rutacridone and rutacridone epoxide was investigated using Salmonella typhimurium without as well as with different metabolic activation systems. Rutacridone epoxide was found to be a direct acting mutagen in S. typhimurium strains TA98, TA100 and TA1538; addition of rat liver preparations resulted in a marked decrease of mutagenicity. In contrast, rutacridone required metabolic conversion to exhibit mutagenic activity. Neither of the compounds had any effect on tester strain TA1978. S9 mixes as well as microsomal and cytosolic preparations from untreated, phenobarbital-treated and 3-methylcholanthrene-treated rats were used to study the activation and deactivation capacities of the enzyme mixtures. In addition, the influence of enzyme inhibitors on the activation and deactivation of the furoacridones were tested. Evidence is presented that rutacridone is metabolized by rat liver enzymes to the corresponding epoxide as the ultimate mutagen.

Mutagenic compounds in an extract from rutae herba (Ruta graveolens L.). I. Mutagenicity is partially caused by furoquinoline alkaloids.

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.