Bridges Bryn A
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
DNA Repair (Amst). 2003 Nov 21;2(11):1269-72. doi: 10.1016/j.dnarep.2003.07.001.
It is a conventional paradigm that mutagens lead to changes in nucleotide sequence when the cell attempts to repair or replicate lesions in DNA (such as adducts or strand breaks) that have been produced by the mutagens or their metabolites. The resulting changes are located at (or very near) the sites of the initial damage. This is the underlying theory behind mutational spectra work, but how general is it in vivo? Work with ionising radiation has shown that there are interesting things going on in the mouse germ line that do not fall within the conventional paradigm. Mutations occur at certain sites remote from initial DNA damage and in greater than expected number. Bryn Bridges discusses some recent papers on mutational changes in the germ line of mice following exposure to chemical mutagens that suggest that such phenomena may not be confined to radiation.
传统观点认为,当细胞试图修复或复制由诱变剂或其代谢产物产生的DNA损伤(如加合物或链断裂)时,诱变剂会导致核苷酸序列发生变化。由此产生的变化位于初始损伤的部位(或非常接近该部位)。这是突变谱研究背后的基本理论,但在体内它的普遍性如何呢?对电离辐射的研究表明,在小鼠生殖系中发生了一些有趣的现象,这些现象并不符合传统模式。突变发生在远离初始DNA损伤的某些位点,且数量超过预期。布林·布里奇斯讨论了一些近期关于小鼠生殖系在接触化学诱变剂后发生突变变化的论文,这些论文表明此类现象可能并不局限于辐射。