Genetic and quantum chemical basis of the mutagenicity of nitroarenes for adenine-thymine base pairs.
The mutagenicity of nitroarenes for Salmonella typhimurium strains with adenine-thymine base pairs at the mutational site is dependent upon enzymic reduction of the nitro function. Although the electrophilic metabolites of nitroarenes are capable of mutating adenine-thymine base pairs, they show a marked preference for guanine-cytosine pairs when given a choice. Quantum chemical calculations indicate the reactivity order for nucleophilic sites in an AT run of base pairs to be the N-7 of adenine (N7(A)) first, followed by an approximately equal reactivity for C-8 of adenine (C8(A)) and O4 of thymine (O4(T)). Given the low probability of reaction of electrophilic metabolites of nitroarenes with adenine-thymine base pairs, the mutagenic potency of nitroarenes for strains with adenine-thymine base pairs at the mutational site is remarkable.
D000225:Adenine; D001483:Base Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D006860:Hydrogen Bonding; D009154:Mutation / Q000187:drug effects*; D009574:Nitro Compounds / Q000633:toxicity*; D011721:Pyrenes / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D013941:Thymine
D009574:Nitro Compounds; D011721:Pyrenes; D000225:Adenine; D013941:Thymine