Mutagenicity of aristolochic acids (I, II) and aristolic acid I in new YG strains in Salmonella typhimurium highly sensitive to certain mutagenic nitroarenes. 1993

E Götzl, and O Schimmer
Institut für Botanik und Pharmazeutische Biologie, Universität Erlangen-Nürnberg, FRG.

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).

UI MeSH Term Description Entries
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D010616 Phenanthrenes POLYCYCLIC AROMATIC HYDROCARBONS composed of three fused BENZENE rings.
D010936 Plant Extracts Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard. Herbal Medicines,Plant Extract,Extract, Plant,Extracts, Plant,Medicines, Herbal
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D012486 Salmonella typhimurium A serotype of Salmonella enterica that is a frequent agent of Salmonella gastroenteritis in humans. It also causes PARATYPHOID FEVER. Salmonella typhimurium LT2
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D034341 Aristolochic Acids Nitro-phenanthrenes occurring in ARISTOLOCHIACEAE and other plants. They derive from stephanine (APORPHINES) by oxidative ring cleavage. The nitro group is a reactive alkylator (ALKYLATING AGENTS) that binds to biological macromolecules. Ingestion by humans is associated with nephropathy (NEPHRITIS). There is no relationship to the similar named aristolochene (SESQUITERPENES).

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