Ruven H J, Berg R J, Seelen C M, Dekkers J A, Lohman P H, Mullenders L H, van Zeeland A A
Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, The Netherlands.
Cancer Res. 1993 Apr 1;53(7):1642-5.
This study describes the induction and repair of UV-induced cyclobutane pyrimidine dimers (CPD) in transcriptionally active and inactive genes in the epidermis of the hairless mouse. Mice were exposed to a single dose of 2000 J/m2 ultraviolet B and kept in darkness for up to 24 h. The CPD frequency was measured in the transcriptionally active hypoxanthine-guanine phosphoribosyltransferase gene, the adenosine deaminase gene, the inactive c-mos protooncogene, and the haptoglobin gene using the CPD-specific enzyme T4 endonuclease V. Sixty % of the CPD was removed from the active genes during the first 4 h, after which no further repair took place up to 24 h. In contrast, the inactive genes did not show any removal of CPD. Assuming that the rate of repair in the c-mos and haptoglobin genes is representative for the repair rate in the genome overall, these results suggest only marginal repair of UV-induced CPD in the mouse epidermis in vivo. The selective repair of active genes in the epidermis of mice resembles that of rodent cells in culture and shows the biological relevance of repair studies performed with cultured rodent cells in vitro.
本研究描述了无毛小鼠表皮中转录活跃和不活跃基因中紫外线诱导的环丁烷嘧啶二聚体(CPD)的诱导和修复情况。小鼠接受单次剂量为2000 J/m2的紫外线B照射,并在黑暗中饲养长达24小时。使用CPD特异性酶T4内切核酸酶V,在转录活跃的次黄嘌呤-鸟嘌呤磷酸核糖转移酶基因、腺苷脱氨酶基因、不活跃的c-mos原癌基因和触珠蛋白基因中测量CPD频率。在最初的4小时内,60%的CPD从活跃基因中被去除,此后直到24小时都没有进一步的修复发生。相比之下,不活跃基因未显示出CPD的任何去除。假设c-mos和触珠蛋白基因中的修复速率代表整个基因组的修复速率,这些结果表明在体内小鼠表皮中紫外线诱导的CPD仅有少量修复。小鼠表皮中活跃基因的选择性修复类似于培养的啮齿动物细胞中的情况,显示了体外培养的啮齿动物细胞进行修复研究的生物学相关性。