Mutagenicity of the 1-nitropyrene-DNA adduct N-(deoxyguanosin-8-yl)-1-aminopyrene in Escherichia coli located in a nonrepetitive CGC sequence

1-Nitropyrene, a common environmental pollutant, forms a major DNA adduct, N-(deoxy-guanosin-8-yl)-1-aminopyrene (dG(AP)). Mutational spectra of rando mly introduced dGAP in Escherichia coli included many different types of mu tations. However, a prior site-specific study in a CGCG(AP)CG sequence show ed only CpG deletions and +1 frame shifts. To further explore the context e ffects of dG(AP) in mutagenesis, in this work this adduct was incorporated into a nonrepetitive CGC sequence in single-stranded M13mp7L2 DNA. Upon rep lication of this construct in repair-competent E. coli, one-base deletions and base substitutions were detected. The -1 frame shifts, whose frequency increased 3-6-fold with SOS (to an average frequency of 1.5%), involved del etion of the adjacent C residues. The base substitutions (similar to 2.2%) included targeted G-to-T and G-to-C transversions, whose frequencies did no t increase with SOS. This suggests that dG(AP) mutagenesis is highly depend ent on the local DNA sequence.