Eastham A M, Atkinson J, West C M
CRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Int J Radiat Biol. 2001 Mar;77(3):295-302. doi: 10.1080/09553000010017108.
To compare clonogenic cell survival, DNA damage and chromosomal radiosensitivity in nine cervix carcinoma cell lines.
Initial and residual (after 24h repair) radiation-induced DNA damage was evaluated using pulsed field gel electrophoresis. Chromosome damage was measured by micronucleus (MN) induction in cytochalasin-B-induced binucleate cells.
Significant differences between the cell lines were obtained in the induced levels of initial damage, residual damage and MN. Values for SF2 for the nine cell lines ranged from 0.36 to 0.92. No correlation was found between clonogenic measurements of radiosensitivity and initial DNA damage dose response slopes. However, borderline significant correlations were seen between clonogenic radiosensitivity data and the levels of residual DNA damage. There was no correlation between clonogenic radiosensitivity and the levels of radiation-induced MN. Cell lines with high levels of initial damage had high yields of MN induced by radiation and the correlation seen was significant.
The poor correlation between the different endpoints precludes their use in a clinical setting on primary tumour samples in vitro. It may be that tumour cell lines in vitro are a poor model for tumours in vivo. Studies aimed at assessing assays for measuring tumour radiosensitivity therefore should employ clinical samples. In vitro cell line work should concentrate on unravelling the complex mechanisms involved in determining a radiosensitive or radioresistant phenotype.
比较九种宫颈癌细胞系的克隆形成细胞存活率、DNA损伤和染色体放射敏感性。
使用脉冲场凝胶电泳评估初始和残留(24小时修复后)辐射诱导的DNA损伤。通过在细胞松弛素B诱导的双核细胞中诱导微核(MN)来测量染色体损伤。
在初始损伤、残留损伤和MN的诱导水平上,细胞系之间存在显著差异。九种细胞系的SF2值范围为0.36至0.92。克隆形成放射敏感性测量与初始DNA损伤剂量反应斜率之间未发现相关性。然而,克隆形成放射敏感性数据与残留DNA损伤水平之间存在临界显著相关性。克隆形成放射敏感性与辐射诱导的MN水平之间没有相关性。初始损伤水平高的细胞系辐射诱导的MN产量高,且观察到的相关性显著。
不同终点之间的相关性较差,这使得它们无法用于体外原发性肿瘤样本的临床环境。体外肿瘤细胞系可能不是体内肿瘤的良好模型。因此,旨在评估测量肿瘤放射敏感性的检测方法的研究应采用临床样本。体外细胞系研究应专注于阐明决定放射敏感或放射抗性表型的复杂机制。