Mutagenicity of nitracrine analogues in Salmonella typhimurium: mutational specificity and activation by bacterial enzymes and rat-liver S9. 1987

L R Ferguson, and P M Turner, and W A Denny

The mutagenic potential of 9-[(3-dimethylaminopropyl)amino]-acridine and its 1-(nitracrine), 2-, 3- and 4-nitro derivatives was studied in several strains of Salmonella typhimurium, using a plate-incorporation assay. In view of the potential importance of DNA binding and nitro group reduction, binding constants and redox potentials were determined. The parent compound was mutagenic only in the frameshift tester strain TA1537, and this effect was not enhanced by the plasmid pKM101. Each of the nitroarenes showed significant activity in S. typhimurium strains TA1537 and TA1538, and this mutagenicity was enhanced by the presence of plasmid pKM101. All caused reversion of the base-pair substitution allele in hisG46 in strain TA100 and this effect was either largely or totally dependent upon the plasmid. The frameshift mutagenic effects of the 3-nitro and 4-nitro compounds appeared to be little dependent upon the classical nitroreductase which is deficient in strain TA98NR, or transacetylase enzyme lacking in strain TA98/1,8-DNP6, whereas the activity of the 1-nitro compound depended partly on that nitroreductase enzyme, and that of the 2-nitro compound on having both activities present. In the latter two cases, the mutagenic effects of the compounds could not be restored by the addition of an S9 mix of mammalian enzymes. Mutagenicity data were compared with physicochemical parameters. The results do not distinguish between the view that the orientation of the nitro group with respect to the aromatic plane dictates mutagenic potential, and the earlier view that the nitro group redox potential is important. However, the extraordinary mutagenic potency of the 1-NO2 derivative is not explainable by its physicochemical properties alone.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
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
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009564 Nitracrine Acridine antineoplastic agent used in mammary and ovarian tumors. It inhibits RNA synthesis. C-283,Ledakrin,C 283,C283
D009601 Nitroreductases Enzymes which reduce nitro groups (NITRO COMPOUNDS) and other nitrogenous compounds. Nitroreductase,Oxidoreductases Acting on other Nitrogenous Compounds as Donors
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
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D000609 Aminoacridines Acridines which are substituted in any position by one or more amino groups or substituted amino groups.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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