No abstract

The mutagenicity of 13 flavonoids has been investigated with the L-arabinose forward mutation assay of Salmonella typhimurium. Each flavonoid was tested by both plate incorporation and preincubation mutagenesis protocols in the presence or the absence of mammalian metabolic activation (S9 mixture). All flavonoids gave a dose-response relationship and induced a number of AraR mutants considered statistically significant. Their minimum mutagenic doses (MMD) differed markedly in the Ara test, covering a 400-fold range: from 4 nmol for quercetin to 1626 nmol for taxifolin. Flavonols were the strongest mutagens, with mutagenic potencies (MMD-1) representing from 27 to approximately 2% that of quercetin. Comparatively, the mutagenicities of other flavonoids represented only less than or equal to 1%. The data reported in this paper for the Ara forward mutation test suggest structural requirements for mutagenicity of bioflavonoids like those previously reported for the His reverse mutation assay: (i) flavonols with a free hydroxyl at position 3 are the strongest mutagenic flavonoids, (ii) saturation of the 2,3 double bond diminishes the mutagenic potency, and (iii) free hydroxyl groups at positions 3' and 4' influence the non-requirement for metabolic activation. The mutagenic properties of quercetin and rutin in the Ara test support the idea that these flavonols are not the major putative mutagens in complex mixtures such as wine.

No abstract

The standard Ames tester strains of Salmonella typhimurium are separated by many steps in their pedigree, some involving mutagen treatments, and contain independently isolated uvrB-bio-gal deletions and rfa mutations. In this work the araD531 mutation was introduced into the Ames tester strains TA100 and TA98. The responsiveness of the resulting strains (BA15 and BA14) to a number of chemical mutagens was then assessed by monitoring the induction of forward mutations to L-arabinose resistance (Ara test). Here we have shown that these two strains of the Ames test differ greatly in their responses to mutagens, in ways that are not associated with the mutagenic specificities of the original his mutations. In general, the genetic background of strain TA100 appears to be more sensitive to the killing effects of chemicals than that of TA98. The greatest differences were found with nifurtimox (NFX) and its analogue, compound 1K. The Ara test responded to the mutagenic effects of these two nitrofurans when carried out in the genetic background of strain TA98 but not in that of TA100. A higher sensitivity to the lethal effects of NFX and 1K together with the greater nitro-reduction capability of strain TA100 as compared with TA98 might explain the differences. In conclusion, our results indicate that the standard Ames S. typhimurium tester strains are not isogenic and that genetic differences at loci other than his might be significant for mutagenicity testing.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract