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

Authors: Skinner, Amy M; Turker, Mitchell S

Published In Photochem Photobiol, (2008 Jan-Feb)

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.

PubMed ID: 18173724

MeSH Terms: Animals; Antioxidants/pharmacology; Cell Line; DNA Repair/genetics*; DNA/genetics*; Hydrogen Peroxide/metabolism; Mice; Mutagenesis*/drug effects; Mutation/genetics*