Wettergren Y, Kullberg A, Levan G
Department of Genetics, University of Gothenburg, Sweden.
Somat Cell Mol Genet. 1994 Jul;20(4):267-85. doi: 10.1007/BF02254717.
In order to investigate whether specific, nonrandom chromosome rearrangements were involved in the induction of hydroxyurea (HU) resistance in mouse SEWA cells, we undertook detailed cytogenetic analyses of three independently selected lines during the long-term treatment with HU. We found that cells with trisomy 12 had selective advantage during early steps of HU treatment. Subsequently, numerous rearrangements of chromosome 12 took place in each of the HU-resistant cell lines. More specifically, the proximal end of chromosome 12 (band A3) was frequently involved in breaks and fusions generating multicentric marker chromosomes. In situ hybridization showed that the functional Rrm2 gene was located in this particular region of chromosome 12. Furthermore, amplification and rearrangements of the structural gene Rrm2 were detected both at the chromosomal and at the molecular level. As discussed, the results of the cytogenetic analyses support the chromosomal breakage model of gene amplification.
为了研究特定的、非随机的染色体重排是否参与了小鼠SEWA细胞中羟基脲（HU）抗性的诱导，我们对三个独立选择的细胞系在长期HU处理过程中进行了详细的细胞遗传学分析。我们发现，12号染色体三体的细胞在HU处理的早期阶段具有选择性优势。随后，在每个HU抗性细胞系中都发生了大量12号染色体的重排。更具体地说，12号染色体的近端（A3带）经常参与断裂和融合，产生多中心标记染色体。原位杂交显示功能性Rrm2基因位于12号染色体的这个特定区域。此外，在染色体和分子水平上都检测到了结构基因Rrm2的扩增和重排。如前所述，细胞遗传学分析结果支持基因扩增的染色体断裂模型。
