Skinner Amy M, Turker Mitchell S
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA.
Photochem Photobiol. 2008 Jan-Feb;84(1):222-7. doi: 10.1111/j.1751-1097.2007.00224.x.
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.
CC到TT的串联突变是由紫外线辐射暴露诱导产生的，不过与更常见的C到T突变相比，其发生频率相对较低。在具有某些基因缺陷的哺乳动物细胞中，紫外线诱导串联突变的情况会增强；然而，尚未描述出能使这种突变在DNA修复功能正常的哺乳动物细胞中频率增加的条件。在本研究中，使用一种能检测小鼠次黄嘌呤磷酸核糖转移酶（Aprt）单个密码子处C到T和CC到TT突变的整合构建体，来检测不同条件下的紫外线B（UVB）诱变情况。以细胞内过氧化氢形式存在的氧化应激增加了UVB诱导的CC到TT突变的频率。令人惊讶的是，细胞单独或联合暴露于两种抗氧化剂（N-乙酰半胱氨酸和生育三烯酚）时，也增强了UVB对CC到TT串联突变的诱导。这些结果首次证明，在DNA修复功能正常的哺乳动物细胞中，UVB诱导的CC到TT串联突变的频率可显著增加，并且表明这种增强效应并不需要对DNA造成直接损伤。
