Kusakabe H, Takahashi T, Tanaka N
Laboratory of Cell Toxicology, Hatano Research Institute/Food and Drug Safety Center, Kanagawa, Japan.
Cytogenet Cell Genet. 1999;85(3-4):212-6. doi: 10.1159/000015295.
To determine the fate of chromosome aberrations induced primarily by clastogenic chemicals, aberrations of chromosome 9 in cultured human peripheral blood lymphocytes were analyzed after exposure to mitomycin C (MMC) at G(0) phase. Chromosome 9 painting by fluorescence in situ hybridization revealed that the translocation of 9p or 9q to another chromosome and the centric fragment representing the entire length of 9p were characteristically generated from chromatid-type aberrations involving the centromeric region of chromosome 9. These changes were not observed at 48 h after culture initiation, but persistently appeared at later stages (72-120 h postinitiation). Induction of centric fragments of 9p and micronuclei without the alpha satellite DNA of chromosome 9 suggested that most of the breaks were induced near the alpha satellite DNA locus on 9q. Modified patterns of chromosome 9 aberrations were also observed, being related to the copy number of the short or long arm of the chromosome. Such unbalanced karyotypes could remain in the lymphocyte genome over further cell divisions for at least 120 h after culture initiation, indicating that these aberrant cells can survive and that they could pose a health risk.
为了确定主要由致断裂化学物质诱导产生的染色体畸变的归宿,在G(0)期将培养的人外周血淋巴细胞暴露于丝裂霉素C(MMC)后,对9号染色体的畸变进行了分析。通过荧光原位杂交进行的9号染色体描绘显示,9p或9q易位至另一条染色体以及代表9p全长的着丝粒片段,典型地是由涉及9号染色体着丝粒区域的染色单体型畸变产生的。这些变化在培养开始后48小时未观察到,但在后期(起始后72 - 120小时)持续出现。9p着丝粒片段和无微卫星DNA的9号染色体微核的诱导表明,大多数断裂是在9q上的α卫星DNA位点附近诱导产生的。还观察到9号染色体畸变的修饰模式,这与染色体短臂或长臂的拷贝数有关。这种不平衡核型在培养开始后至少120小时的进一步细胞分裂过程中可能会保留在淋巴细胞基因组中,表明这些异常细胞能够存活并且可能构成健康风险。