Radiation-induced mutations at the autosomal thymidine kinase locus are not elevated in p53-null cells.
Radiation-induced mutations at the autosomal thymidine kinase locus are not elevated in p53-null cells.
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DOI：
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发表时间：
1999-07
期刊：
影响因子：
11.2
通讯作者：
Y. Chuang;Q. Chen;J. Brown;J. Sedivy;H. Liber
中科院分区：
文献类型：
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作者：
Y. Chuang;Q. Chen;J. Brown;J. Sedivy;H. Liber
为了进一步探索某些形式的突变的p53可以以积极的方式增加诱变的可能性，使用无启动子的基因靶向方法创建了双p53敲除细胞系。通过Southern印迹和Western印迹分析证实这些p53-null细胞的身份。辐射诱导的毒性和致突变性之间进行了比较p53-null细胞，TK 6细胞与野生型p53，和WTK 1细胞与p53点突变的密码子237。在常染色体，杂合子胸苷激酶基因座，p53-null细胞具有相同的背景突变频率和TK 6大约同样可变，而WTK 1是更敏感的自发产生和X射线诱导的突变。因此，这些结果表明野生型p53的缺乏不会导致突变增加。
To explore further the possibility that some forms of mutated p53 may increase mutagenesis in a positive manner, a double p53 knockout cell line was created, using a promoterless gene targeting approach. The identity of these p53-null cells was confirmed by Southern blot and Western blot analyses. Radiation-induced toxicity and mutagenicity was then compared among p53-null cells, TK6 cells with wild-type p53, and WTK1 cells with a p53 point mutation in codon 237. At the autosomal, heterozygous thymidine kinase locus, p53-null cells had equivalent background mutation frequencies and were approximately equally mutable as TK6, whereas WTK1 was much more sensitive to spontaneously arising and X-ray-induced mutation. Thus, these results indicate that the lack of wild-type p53 did not lead to increased mutagenesis.