Khodarev N N, Park J O, Yu J, Gupta N, Nodzenski E, Roizman B, Weichselbaum R R
Department of Radiation and Cellular Oncology and The Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637, USA.
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12665-70. doi: 10.1073/pnas.211443698.
U87 cells derived from human malignant gliomas and growtharrested human embryonic lung (HEL) fibroblasts were examined with respect to their response to ionizing radiation by profiling their RNAs. In the first series of experiments, cells grown in vitro were harvested and the RNAs were extracted 5 h after exposure to 1, 3, or 10 Gy. In the second series of experiments the U87 tumors were implanted in nude mice and subjected to the same doses of irradiation. The xenografts were harvested at 1, 5, or 24 h after irradiation and subjected to the same analyses. We observed and report on (i) cell-type common and cell-type specific responses, (ii) genes induced at low levels of irradiation but not at higher doses, (iii) temporal patterns of gene response in U87 xenografts that varied depending on radiation dose and temporal patterns of response that were similar at all doses tested, (iv) significantly higher up-regulation of cells in xenografts than in in vitro cultures, and (v) genes highly up-regulated by radiation. The responding genes could be grouped into nine functional clusters. The representation of the nine clusters was to some extent dependent on dose and time after irradiation. The results suggest that clinical outcome of ionizing radiation treatment may benefit significantly by taking into account both cell-type and radiation-dose specificity of cellular responses.
通过对RNA进行分析，研究了源自人类恶性胶质瘤的U87细胞以及生长停滞的人类胚胎肺（HEL）成纤维细胞对电离辐射的反应。在第一系列实验中，收获体外培养的细胞，并在暴露于1、3或10 Gy辐射后5小时提取RNA。在第二系列实验中，将U87肿瘤植入裸鼠体内，并给予相同剂量的辐射。在辐射后1、5或24小时收获异种移植瘤，并进行相同的分析。我们观察并报告了：（i）细胞类型共同和细胞类型特异性反应；（ii）低剂量辐射诱导但高剂量未诱导的基因；（iii）U87异种移植瘤中基因反应的时间模式，其因辐射剂量而异，以及在所有测试剂量下相似的反应时间模式；（iv）异种移植瘤中的细胞上调明显高于体外培养；（v）辐射高度上调的基因。反应基因可分为九个功能簇。九个簇的表现程度在一定程度上取决于辐射剂量和辐射后的时间。结果表明，考虑细胞反应的细胞类型和辐射剂量特异性可能会显著有益于电离辐射治疗的临床结果。
