Jung H, Krüger H J, Brammer I, Zywietz F, Beck-Bornholdt H P
Institute of Biophysics and Radiobiology, University of Hamburg, Federal Republic of Germany.
Int J Radiat Biol. 1990 Mar;57(3):567-89. doi: 10.1080/09553009014552701.
The kinetics of depopulation and repopulation of the solid transplantable rhabdomyosarcoma R1H of the rat following local irradiation with single subcurative X-ray doses of 7.5, 15 and 30 Gy was studied. Several parameters were sequentially measured over a time interval of 4 weeks after irradiation: the ratio of the number of tumour to host cells, and the cellular DNA content of tumour and host cells, were determined by flow cytometry; the amount of DNA per gram of tumour tissue was determined biochemically; the clonogenic fraction of tumour cells was obtained from in vitro colony assay; and the tumour volume was assessed by in situ caliper measurements. From the amount of DNA per gram and the average DNA content per cell, the total number of cells per gram of tumour tissue was obtained. From this and the other parameters measured, the number of clonogenic tumour cells, non-clonogenic tumour cells and nucleated host cells per tumour, as well as their variation with time and dose, could be derived. The results showed that there was a lag period prior to depopulation amounting to 3.8 +/- 1.4, 1.4 +/- 0.8 or 0 +/- 0.7 days for 7.5, 15 or 30 Gy, respectively. The rate of depopulation of non-clonogenic tumour cells increased with dose; the halving times of non-clonogens were 4.7 +/- 1.8, 2.6 +/- 0.7 or 2.1 +/- 0.4 days for the three doses applied. There were no indications that proliferation of doomed cells contributed significantly to tumour growth after irradiation. After lag periods that were similar in length to those prior to depopulation, a massive immigration of host cells was observed. Under certain conditions more than 97 per cent of the cells present in irradiated tumours were found to be of host origin. There was a lag period before the onset of repopulation by clonogenic tumour cells, the length of which increased from 2.7 +/- 0.7 to 5.0 +/- 0.8 or 6.3 +/- 1.0 days for 7.5, 15 or 30 Gy, respectively. The initial rate of repopulation increased with radiation dose; after the end of the lag period the doubling time of clonogenic tumour cells (in controls amounting to 3.7 +/- 0.2 days) was 3.1 +/- 0.1, 2.1 +/- 0.1 and 1.1 +/- 0.1 days for the three doses applied.(ABSTRACT TRUNCATED AT 400 WORDS)
研究了大鼠可移植实体横纹肌肉瘤R1H在单次亚治愈剂量7.5、15和30 Gy局部X线照射后细胞减少和再增殖的动力学。在照射后的4周时间间隔内依次测量了几个参数：通过流式细胞术测定肿瘤细胞与宿主细胞数量之比以及肿瘤细胞和宿主细胞的细胞DNA含量；通过生化方法测定每克肿瘤组织的DNA量；通过体外集落测定获得肿瘤细胞的克隆形成分数；通过原位卡尺测量评估肿瘤体积。根据每克DNA量和每个细胞的平均DNA含量，得出每克肿瘤组织的细胞总数。由此以及所测量的其他参数，可以得出每个肿瘤中克隆形成肿瘤细胞、非克隆形成肿瘤细胞和成核宿主细胞的数量，以及它们随时间和剂量的变化。结果表明，细胞减少之前存在一个滞后期，7.5、15或30 Gy剂量的滞后期分别为3.8±1.4、1.4±0.8或0±0.7天。非克隆形成肿瘤细胞的减少速率随剂量增加；应用的三种剂量下非克隆形成细胞的减半时间分别为4.7±1.8、2.6±0.7或2.1±0.4天。没有迹象表明注定死亡的细胞增殖对照射后肿瘤生长有显著贡献。在与细胞减少之前长度相似的滞后期之后，观察到宿主细胞大量迁入。在某些条件下，发现照射后肿瘤中存在的细胞超过97%是宿主来源的。克隆形成肿瘤细胞再增殖开始之前存在一个滞后期，7.5、15或30 Gy剂量下滞后期的长度分别从2.7±0.7天增加到5.0±0.8天或6.3±1.0天。再增殖的初始速率随辐射剂量增加；滞后期结束后，应用的三种剂量下克隆形成肿瘤细胞的倍增时间（对照中为3.7±0.2天）分别为3.1±0.1、2.1±0.1和1.1±0.1天。（摘要截断于400字）
