Lavin M F, Bennett I, Ramsay J, Gardiner R A, Seymour G J, Farrell A, Walsh M
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
J Natl Cancer Inst. 1994 Nov 2;86(21):1627-34. doi: 10.1093/jnci/86.21.1627.
The description of genes and genetic syndromes, such as ataxia-telangiectasia, that predispose some women to breast cancer will provide greater insight into the genetic basis of cancer susceptibility.
Our goal was to establish cell lines from patients with breast and bladder cancers, to screen for enhanced levels of radiation-induced arrest in the G2 phase of the cell cycle such as is observed in ataxia-telangiectasia heterozygotes, and to correlate G2 arrest with other prognostic indicators of these cancers and in vivo radiosensitivity.
Epstein-Barr virus-transformed lymphoblastoid cells were established from 108 female patients with breast cancer and 24 age-matched female control subjects, and from 45 patients with bladder cancer and 18 age-matched control subjects. Cells were exposed to 3 Gy of gamma radiation, and the percentages of cells in G1 and G2 phases were determined at 18 and 24 hours after irradiation by fluorescence-activated cell sorter analysis. Postirradiation delay in G2 phase was determined by calculating the percentage of cells in G2 and by using the ratio G2/G1.
When we determined the percentage of cells in G2 phase at 18 hours after irradiation in 108 lymphoblastoid cells from breast cancer patients, we observed an increase of between 3% and 38% in the number of cells in G2 phase in comparison with cells that were not irradiated. Comparison with previous G2-phase arrest data for ataxia-telangiectasia heterozygotes using a cutoff point at 29% delay demonstrated that 20% and 8% of the breast cancer cell lines of the case patients and control subjects, respectively, fell into that category (P < .001). At the same time after irradiation, it was not possible to distinguish between bladder cancer cell lines (7%) and those of the corresponding control group (6%). Assessment of radiation effects by G2/G1 ratio showed that 18% of the breast cancer patients and 8% of the control subjects were in the high range. When G2 arrest was correlated with other prognostic factors, we found that case patients with a greater G2 block were more likely to have had a family history of breast cancer (P < .006) and more aggressive tumors when assessed by number of involved lymph nodes (P < .002) and tumor size (P < .05). Furthermore, an adverse response to radiotherapy was observed in a group of patients with high G2 arrest.
While the postirradiation increase in G2-phase arrest in cells from breast cancer patients observed in this study may indicate genetic heterozygosity for ataxia-telangiectasia, it might also reflect other genetic abnormalities important to breast cancer.
对诸如共济失调毛细血管扩张症等使一些女性易患乳腺癌的基因和遗传综合征的描述，将能更深入地了解癌症易感性的遗传基础。
我们的目标是从乳腺癌和膀胱癌患者中建立细胞系，筛选细胞周期G2期辐射诱导的阻滞水平增强的情况（如在共济失调毛细血管扩张症杂合子中观察到的那样），并将G2期阻滞与这些癌症的其他预后指标以及体内放射敏感性相关联。
从108例女性乳腺癌患者和24例年龄匹配的女性对照受试者，以及45例膀胱癌患者和18例年龄匹配的对照受试者中建立爱泼斯坦 - 巴尔病毒转化的淋巴母细胞系。细胞暴露于3 Gy的γ辐射，通过荧光激活细胞分选分析在照射后18小时和24小时测定G1期和G2期细胞的百分比。通过计算G2期细胞的百分比并使用G2/G1比率来确定照射后G2期的延迟。
当我们在照射后18小时测定108例乳腺癌患者的淋巴母细胞系中G2期细胞的百分比时，我们观察到与未照射的细胞相比，G2期细胞数量增加了3%至38%。与共济失调毛细血管扩张症杂合子先前的G2期阻滞数据进行比较，使用29%延迟的截止点表明，病例患者和对照受试者的乳腺癌细胞系分别有20%和8%属于该类别（P <.001）。在照射后的同一时间，无法区分膀胱癌细胞系（7%）和相应对照组的细胞系（6%）。通过G2/G1比率评估辐射效应表明，18%的乳腺癌患者和8%的对照受试者处于高范围。当G2期阻滞与其他预后因素相关联时，我们发现G2期阻滞程度更高的病例患者更有可能有乳腺癌家族史（P <.006），并且通过受累淋巴结数量（P <.002）和肿瘤大小（P <.05）评估时肿瘤更具侵袭性。此外，在一组G2期阻滞程度高的患者中观察到对放疗的不良反应。
虽然本研究中观察到乳腺癌患者细胞照射后G2期阻滞增加可能表明存在共济失调毛细血管扩张症的遗传杂合性，但它也可能反映了对乳腺癌重要的其他遗传异常。
