Puerto S, Surrallés J, Ramírez M J, Carbonell E, Creus A, Marcos R
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
Mutat Res. 1999 Feb 2;439(1):3-11. doi: 10.1016/s1383-5718(98)00169-7.
The genomic frequency of chromosomal aberrations obtained by chromosome painting is usually extrapolated from the observed frequency of aberrations by correcting for the DNA content of the labelled chromosomes. This extrapolation is based upon the assumption of random distribution of breakpoints from which aberrations are generated. However, the validity of this assumption has been widely questioned. While extensive investigations have been performed with ionizing radiation as chromosome breaking agent, little efforts have been done with chemical clastogens. In order to investigate interchromosomal differences in chemically-induced chromosome damage, we have used multicolour chromosome painting to analyse bleomycin-induced aberrations involving chromosomes 1 and 4, two chromosomes that differ in gene density. In addition, we have measured the effect of cytosine arabinoside upon the repair of bleomycin-induced DNA damage in chromosomes 1 and 4. Our results show that these chromosomes are equally sensitive to the clastogenic effect of bleomycin with a similar linear dose-effect relationship. However, the high gene density chromosome 1 appeared to be more sensitive to repair inhibition by Ara-C than chromosome 4. This enhanced sensitivity to repair inhibition in chromosome 1 could be mediated by preferential repair of open chromatin and actively transcribed regions.
通过染色体涂染获得的染色体畸变的基因组频率通常是通过校正标记染色体的DNA含量，从观察到的畸变频率推断出来的。这种推断基于产生畸变的断点随机分布的假设。然而，这一假设的有效性受到了广泛质疑。虽然已经对作为染色体断裂剂的电离辐射进行了广泛研究，但对化学断裂剂的研究却很少。为了研究化学诱导的染色体损伤中的染色体间差异，我们使用多色染色体涂染来分析博来霉素诱导的涉及1号和4号染色体的畸变，这两条染色体在基因密度上有所不同。此外，我们还测量了阿糖胞苷对1号和4号染色体中博来霉素诱导的DNA损伤修复的影响。我们的结果表明，这些染色体对博来霉素的断裂效应同样敏感，具有相似的线性剂量效应关系。然而，基因密度高的1号染色体似乎比4号染色体对阿糖胞苷的修复抑制更敏感。1号染色体对修复抑制的这种增强敏感性可能是由开放染色质和活跃转录区域的优先修复介导的。
