Auer H, Oehler R, Lindner R, Kowalski H, Sliutz G, Orel L, Kucera E, Simon M M, Glössl J
Centre of Applied Genetics, Univ. BOKU, Vienna, Austria.
Mutat Res. 1997 Sep 18;393(1-2):165-73. doi: 10.1016/s1383-5718(97)00102-2.
The genotoxic properties of 2',2'-difluorodeoxycytidine (dFdC) were characterised using diploid, mortal low-passage fibroblasts (LPF cells) and the spontaneously transformed fibroblast cell line V79. In both cell types, incorporation of dFdC into the DNA led to an increase of DNA single-strand breaks evaluated by an in situ nick translation assay and to an accumulation of cells in the S-phase of the cell cycle. At concentrations below those leading to cell cycle arrest, dFdC neither induced sister chromatid exchange (SCE) nor structural chromosome aberrations in LPF cells, whereas V79 cells accumulated SCEs as well as chromosome breaks over a broad dose range. In LPF cells treated with dFdC, chromosomal alterations were detected by the micronucleus assay within a narrow concentration range, whereas in V79 cells, a dose-dependent increase in the appearance of micronuclei was seen up to cytotoxic concentrations. In addition, V79 cells went into apoptosis, as evaluated by nuclear fragmentation and condensation, whereas this phenomenon was not detectable in LPF cells.
使用二倍体、有限传代的低代次成纤维细胞（LPF细胞）和自发转化的成纤维细胞系V79对2',2'-二氟脱氧胞苷（dFdC）的遗传毒性特性进行了表征。在这两种细胞类型中，dFdC掺入DNA导致通过原位缺口平移试验评估的DNA单链断裂增加，并导致细胞在细胞周期的S期积累。在导致细胞周期停滞的浓度以下，dFdC在LPF细胞中既不诱导姐妹染色单体交换（SCE），也不诱导染色体结构畸变，而V79细胞在很宽的剂量范围内积累SCE和染色体断裂。在用dFdC处理的LPF细胞中，在狭窄的浓度范围内通过微核试验检测到染色体改变，而在V79细胞中，直到细胞毒性浓度，微核出现呈剂量依赖性增加。此外，通过核碎片化和凝聚评估，V79细胞发生凋亡，而在LPF细胞中未检测到这种现象。
