| dc.description |
The mutagenic activity of a series of longer chain O<sup>6</sup>-n-alkylguanine residues (O<sup>6</sup>-n-propyl, O<sup>8</sup>-n-butyl, O<sup>6</sup>-n-octyl) has been analyzed using a plasmid molecule (pUC 9) in which single O<sup>6</sup>alkylguanines were positioned in the unique Pstl recognition site by shot gun ligation (Nucleic Acids Res. 13, 3305-3316 (1985)) of overlapping synthetic oligonucleotides. After transfection of these vectors into E.coli cells having normal DNA repair systems, progeny plasmids were produced, of which 2.6%, 2.8% and 4.3% were mutated in their Pstl site when containing O<sup>6</sup>-npropylguanine, O<sup>6</sup>-n-butylguanine, O<sup>6</sup>-n-octylguanine, respectively. DNA sequence analysis of mutant plasmid genomes revealed that O<sup>8</sup>-n-propylguanine and O<sup>6</sup>-nbutylguanine induced exclusively G–A transitions located specifically at the preselected site. O<sup>6</sup>-noctylguanine induced apart from G–A transitions (70%) also targeted G–T transversions (30%). These results indicate that the mutation frequency of longer chain O<sup>6</sup>-alkylguanines can be substantial in cells with normal repair systems and that the mutation pattern depends on the nature of the alkyl group. |
