High frequency induction of CC to TT tandem mutations in DNA repair-proficient mammalian cells

Amy M. Skinner, Mitchell S. Turker

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The CC to TT tandem mutation is induced by UV radiation exposure, though at relatively low frequencies when compared with the more commonly induced C to T mutation. Induction of the tandem mutation by UV is enhanced in mammalian cells with certain genetic deficiencies; however, conditions have not been described in which the frequency of this mutation is enhanced in DNA repair-proficient mammalian cells. For this study, an integrated construct that detects C to T and CC to TT mutations at a single codon in mouse Aprt was used to examine UVB mutagenesis under various conditions. Oxidative stress, in the form of intracellular hydrogen peroxide, increased the frequency of UVB-induced CC to TT mutations. Surprisingly, exposure of the cells to two antioxidants (N-acetylcysteine and trolox), either alone or in combination, also enhanced UVB induction of CC to TT tandem mutations. These results demonstrate, for the first time, that the frequency of UVB-induced CC to TT tandem mutations can be enhanced dramatically in DNA repair-proficient mammalian cells, and suggest that the enhancing effect does not require direct damage to DNA.

Original languageEnglish (US)
Pages (from-to)222-227
Number of pages6
JournalPhotochemistry and photobiology
Volume84
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry

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