Mutagenicity of aristolochic acids (I, II) and aristolic acid I in new YG strains in Salmonella typhimurium highly sensitive to certain mutagenic nitroarenes.
Aristolochic acid I and II, two naturally occurring nitroaromatics, were studied for their mutagenicity in Salmonella typhimurium tester strains YG1020, 1021, 1024, 1025, 1026 and 1029 without exogenous metabolic activation. These strains contain multicopy plasmids which carry the genes for the classical bacterial nitroreductase or O-acetyltransferase. The strains TA98, TA100 and TA1537 were included in the study for comparison. Aristolic acid I, the analogue lacking the nitro group, and its sodium salt were also tested. Both aristolochic acids revealed mutagenicity in the respective YG strains derived from TA100, but the effect was no stronger than with the parent strain. Only weak activity was observed in TA98 and some YG strains derived from it. Aristolochic acid II was generally the more active compound. Aristolic acid I and its sodium salt did not exhibit any mutagenicity in any tester strain. From the results the following conclusions were drawn. (i) Only the nitro group is important for the mutagenicity of the aristolochic acids in S. typhimurium. (ii) It is suggested that aristolochic acid II is so efficiently metabolized by the classical bacterial nitroreductase that the additional activity produced from the YG strains no longer affects the metabolic activation. (iii) The methoxy group is probably responsible for the lower activity of aristolochic acid I, producing steric hindrance for binding of the genetically active intermediate to DNA or for binding of the substrate to the active site of the enzyme(s).
Götzl
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E
Institut für Botanik und Pharmazeutische Biologie, Universität Erlangen-Nürnberg, FRG.
Schimmer
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O
D034341:Aristolochic Acids; D004249:DNA Damage; D009152:Mutagenicity Tests; D010616:Phenanthrenes / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D010957:Plasmids; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship
D034341:Aristolochic Acids; D010616:Phenanthrenes; D010936:Plant Extracts; C018834:aristolic acid; C000228:aristolochic acid I; C042310:aristolochic acid II