Scott D, Barber J B, Spreadborough A R, Burrill W, Roberts S A
Int J Radiat Biol. 1999 Jan;75(1):1-10. doi: 10.1080/095530099140744.
It has been shown previously that sensitivity to the induction of chromosome damage by ionizing radiation is, on average, higher in G2 or G0 lymphocytes of breast cancer patients than of normal healthy controls. The authors suggested that elevated chromosomal radiosensitivity may be a marker for breast cancer predisposition. To investigate whether the G0 micronucleus assay is a true surrogate for the more demanding G2 metaphase assay, both tests have now been performed on the same blood samples from 80 patients.
For the G0 micronucleus assay, cells were exposed to 3.5 Gy 137Cs gamma-rays 6 h before mitogenic stimulation, treated with cytochalasin B at 24 h post-stimulation and harvested at 90 h. For the G2 assay, at 72 h after stimulation cells were given 0.5 Gy X-rays and harvested 90 min later.
Previous observations were confirmed, now with much larger numbers of donors, in that approximately 40% of breast cancer patients showed elevated sensitivity in the G2 assay (135 patients, 105 normals) and 25% in the G0 assay (130 patients, 68 normals). However, there was no correlation between G2 and G0 sensitivity for the 80 patients tested (r = -0.001, p = 0.99). Most of the sensitive patients were either G2 or G0 sensitive, with only 4% sensitive in both assays.
The results suggest that different mechanisms of chromosomal radiosensitivity operate in G2 and G0 cells and that, in general, each chromosomally radiosensitive patient is defective in only one such mechanism, possibly via mutation (or polymorphism) of a single gene. Such mutations may confer cancer predisposition, of low penetrance, in a substantial proportion of patients.
先前的研究表明，平均而言，乳腺癌患者G2期或G0期淋巴细胞对电离辐射诱导的染色体损伤的敏感性高于正常健康对照者。作者认为染色体辐射敏感性升高可能是乳腺癌易感性的一个标志。为了研究G0微核试验是否是更严格的G2中期试验的真正替代方法，现在对80名患者的相同血样进行了这两种试验。
对于G0微核试验，细胞在有丝分裂刺激前6小时暴露于3.5 Gy 137Csγ射线，刺激后24小时用细胞松弛素B处理，并在90小时收获。对于G2试验，在刺激后72小时给细胞0.5 Gy X射线，并在90分钟后收获。
先前的观察结果得到了证实，现在有更多的供体，即大约40%的乳腺癌患者在G2试验中表现出敏感性升高（135例患者，105例正常对照），25%在G0试验中表现出敏感性升高（130例患者，68例正常对照）。然而，对于所测试的80名患者，G2和G0敏感性之间没有相关性（r = -0.001，p = 0.99）。大多数敏感患者要么是G2敏感，要么是G0敏感，只有4%在两种试验中都敏感。
结果表明，G2期和G0期细胞中染色体辐射敏感性的机制不同，并且一般来说，每个染色体辐射敏感的患者仅在一种这样的机制中存在缺陷，可能是通过单个基因的突变（或多态性）。这种突变可能在相当比例的患者中赋予低外显率的癌症易感性。
