The 4-nitroquinoline 1-oxide mutational spectrum in single stranded DNA is characterized by guanine to pyrimidine transversions.
4-Nitroquinoline-1-oxide is a potent mutagen and carcinogen which induces two main guanine adducts at positions C8 and N2. In ds or ss damaged DNA the ratio C8/N2 adducts is 1:2 and 8-10:1, respectively. In bacteria and yeast 4NQO has been shown to be a base substitution mutagen acting at G residues inducing mainly G to A transitions. We determined the mutational spectrum induced by the 4NQO metabolite, acetoxy-4-aminoquinoline 1-oxide, in the M13lacZ'/E. coli lacZ delta M15 alpha complementation assay using ssDNA. Among 68 Ac-4HAQO induced mutants, G to Pyr transversion was the most frequent base substitution observed. By comparison with dsDNA based systems, our data suggest that dGuo-C8-AQO induces G to Pyr transversions. A mechanism to explain how this lesion may induce transversions is proposed.
Fronza
G
G
Laboratory of Mutagenesis, National Institute for Research on Cancer (IST), Genova, Italy.
Campomenosi
P
P
Iannone
R
R
Abbondandolo
A
A
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D001483:Base Sequence; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004269:DNA, Bacterial / Q000737:chemistry / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000187:drug effects*; D004926:Escherichia coli / Q000235:genetics; D006147:Guanine / Q000737:chemistry; D008969:Molecular Sequence Data; D011743:Pyrimidines / Q000737:chemistry; D014162:Transfection
D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D011743:Pyrimidines; D015112:4-Nitroquinoline-1-oxide; D006147:Guanine