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The 4-nitroquinoline 1-oxide mutational spectrum in single stranded DNA is characterized by guanine to pyrimidine

G Fronza1, P Campomenosi, R Iannone

  • 1Laboratory of Mutagenesis, National Institute for Research on Cancer (IST), Genova, Italy.

Nucleic Acids Research
|March 25, 1992
PubMed

Insights

Acetoxy-4-aminoquinoline 1-oxide (Ac-4HAQO), a metabolite of 4-Nitroquinoline-1-oxide, is a potent mutagen. This study found it primarily causes Guanine to Pyrimidine (G to Pyr) transversions in single-stranded DNA (ssDNA).

Area of Science:

  • Molecular biology
  • Toxicology
  • Genetics

Background:

  • 4-Nitroquinoline-1-oxide (4NQO) is a known mutagen and carcinogen.
  • 4NQO induces guanine adducts at C8 and N2 positions in DNA.
  • 4NQO acts as a base substitution mutagen in bacteria and yeast, primarily causing G to A transitions.

Purpose of the Study:

  • To determine the mutational spectrum induced by the 4NQO metabolite, acetoxy-4-aminoquinoline 1-oxide (Ac-4HAQO).
  • To investigate the mutagenic mechanism of Ac-4HAQO in single-stranded DNA (ssDNA).

Main Methods:

  • Utilized the M13lacZ'/E. coli lacZ delta M15 alpha complementation assay.
  • Applied the assay using ssDNA to analyze mutations induced by Ac-4HAQO.
  • Determined the frequency and type of base substitutions in induced mutants.

Main Results:

  • Ac-4HAQO induced 68 mutants in the M13lacZ' system.
  • Guanine to Pyrimidine (G to Pyr) transversion was the most frequent base substitution observed.
  • Data suggests that the guanine-C8-adduct (dGuo-C8-AQO) induces G to Pyr transversions in ssDNA.

Conclusions:

  • Ac-4HAQO is a potent mutagen inducing predominantly G to Pyr transversions in ssDNA.
  • The findings provide insights into the mechanism of 4NQO-induced mutagenesis.
  • Comparison with double-stranded DNA (dsDNA) systems highlights differences in mutagenic outcomes based on DNA structure.

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