HETEROGENEITY IN THE CLASTOGENIC RESPONSE TO X-RAYS IN LYMPHOCYTES FROM ATAXIA-TELANGIECTASIA HETEROZYGOTES AND CONTROLS
HETEROGENEITY IN THE CLASTOGENIC RESPONSE TO X-RAYS IN LYMPHOCYTES FROM ATAXIA-TELANGIECTASIA HETEROZYGOTES AND CONTROLS
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DOI：
10.1007/bf00124257
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发表时间：
1992-05-01
影响因子：
2.3
通讯作者：
KELSEY, KT
中科院分区：
文献类型：
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作者：
WIENCKE, JK;WARA, DW;KELSEY, KT
对45例正常人和19例共济失调-毛细血管扩张症(A-T)杂合子的淋巴细胞培养中X射线诱发的染色单体畸变率进行了编码分析。在研究人群中，60cGyX射线在细胞周期的G2晚期诱导的染色单体断裂呈双峰分布。在6个对照组(13%)和19个A-T杂合子中的12个(63%)中，观察到的X射线诱发的断裂率处于较高的分布模式。然而，来自A-T杂合子的淋巴细胞对60cGy射线诱发的染色单体断裂敏感，但在20cGy射线照射后并没有增加畸变率。在杂合子中没有观察到A-T纯合子中出现的对DNA合成的辐射抗性抑制。共培养实验表明，来自A-T杂合子的淋巴细胞含有X射线诱导的染色单体断裂增加的G2延迟。结果显示A-T杂合性与G2染色体敏感性显著相关(P<；0.001；Wilcoxon秩和检验)。然而，对X射线诱导的断裂的测量未能识别所测试的A-T杂合子中的37%。对照组中对X射线敏感性增加的预测患病率大约是一般人群中A-T杂合子估计频率的3到30倍。因此，尽管对X射线诱导的染色单体断裂的敏感性增加似乎与A-T-基因有关，但它不是A-T杂合性的可靠指标。除了A-T基因以外的遗传或环境因素也必须参与增加的碎裂反应。
A coded analysis of X-ray-induced chromatid aberrations in lymphocyte cultures from 45 control individuals and 19 ataxia-telangiectasia (A-T) heterozygotes was performed. The distribution of chromatid breaks induced in the late G2 portion of the cell cycle by 60 cGy of X-rays appeared bimodal in the study population. In six controls (13 percent) and in 12 of 19 (63 percent) A-T heterozygotes, the yields of X-ray-induced breaks observed were within the higher mode of the distribution. However, lymphocytes from A-T heterozygotes sensitive to the induction of chromatid breaks by 60 cGy did not contain increased numbers of aberrations following exposure to 20 cGy. The radio-resistant inhibition of DNA synthesis that occurs in A-T homozygotes was not observed in heterozygotes. Co-cultivation experiments showed an increased G2 delay in lymphocytes from an A-T heterozygote whose lymphocytes contained increased X-ray-induced chromatid breaks. The results show a significant association of A-T heterozygosity with G2 chromosomal sensitivity (P < 0.001; Wilcoxon rank sum test). The measurement of X-ray-induced breaks, however, failed to identify 37 percent of A-T heterozygotes tested. The predicted prevalence of increased sensitivity to X-rays in controls is approximately three- to 30-fold greater than the estimated frequency of A-T heterozygotes in the general population. Therefore, although the increased sensitivity to X-ray-induced chromatid breaks appears to be associated with the A-T-gene, it is not a reliable indicator of A-T heterozygosity. Genetic or environmental factors other than the A-T gene also must be involved in the increased clastogenic response.