High frequency induction of CC to TT tandem mutations in DNA repair-proficient mammalian cells.
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.
Skinner
Amy M
AM
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA.
Turker
Mitchell S
MS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D004247:DNA / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D016296:Mutagenesis / Q000187:drug effects; D009154:Mutation / Q000235:genetics*
D000975:Antioxidants; D004247:DNA; D006861:Hydrogen Peroxide