Urano M, Nishimura Y, Kuroda M, Reynolds R
Department of Radiation Medicine, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Radiother Oncol. 1998 Aug;48(2):221-8. doi: 10.1016/s0167-8140(98)00010-3.
To investigate the significance of hypoxic cells, reoxygenation and repopulation for the outcome of fractionated radiotherapy of a slow-growing subline of a murine fibrosarcoma and to compare the results with those previously obtained from the original fast-growing tumor.
A slow-growing subline, 457-O, was obtained among the tumors that recurred after a single irradiation to the third generation isotransplants of a mouse fibrosarcoma, FSa-II. The single cell suspensions were transplanted into the mouse foot and when the tumors reached an average diameter of 4 mm, they were subjected to one to 20 equal daily y-ray doses given in air (A) or under hypoxic conditions (H). The TCD50 (50% tumor control radiation dose) was calculated according to the tumor control frequency within 180 days. The linear-quadratic plus time model was fitted to these data by logistic regression analysis.
The volume doubling time of the 457-O tumors was approximately 2.2 times slower than that of the original FSa-II tumors. The TCD50(H) (single dose) was 52.3 Gy and increased with an increasing number of fractions to a TCD50(H) (20 doses) of 90.8 Gy. This increase of 38.5 Gy was much smaller than that of 149 Gy for the original FSa-II. The TCD50(A) (single dose) and TCD50(A) (20 doses) were 41.3 and 50.6 Gy, respectively. This small difference of 9.3 Gy contrasted with a significant increase of 52.9 Gy for the FSa-II.
These results suggested no repopulation of 457-O tumor clonogens during the course of up to 20 daily doses, while the original FSa-II tumor cells repopulated substantially. Hypoxic clonogens in the slow-growing tumor reoxygenated but some fractions remained critical.
The present data together with those obtained from the fast-growing FSa-II suggested that hypoxic clonogens were critical for the outcome of fractionated radiotherapy. Repopulation was insignificant in this slow-growing tumor during five to 20 daily doses.
研究低氧细胞、再氧合和再增殖对小鼠纤维肉瘤生长缓慢亚系分次放疗结果的意义，并将结果与先前从原始快速生长肿瘤中获得的结果进行比较。
在对小鼠纤维肉瘤FSa-II的第三代同基因移植瘤单次照射后复发的肿瘤中获得了一个生长缓慢的亚系457-O。将单细胞悬液接种到小鼠足部，当肿瘤平均直径达到4mm时，对其进行1至20次每日均等的γ射线照射，照射在空气中（A）或低氧条件下（H）进行。根据180天内的肿瘤控制频率计算TCD50（50%肿瘤控制辐射剂量）。通过逻辑回归分析将线性二次加时间模型拟合到这些数据。
457-O肿瘤的体积倍增时间比原始FSa-II肿瘤慢约2.2倍。TCD50（H）（单次剂量）为52.3Gy，随着分次次数增加至TCD50（H）（20次剂量）为90.8Gy。增加的38.5Gy远小于原始FSa-II的149Gy。TCD50（A）（单次剂量）和TCD50（A）（20次剂量）分别为41.3和50.6Gy。9.3Gy的微小差异与FSa-II的显著增加52.9Gy形成对比。
这些结果表明，在多达20次每日剂量的过程中，457-O肿瘤克隆原没有再增殖，而原始FSa-II肿瘤细胞大量再增殖。生长缓慢肿瘤中的低氧克隆原发生了再氧合，但仍有一些分次保持临界状态。
目前的数据以及从快速生长的FSa-II获得的数据表明，低氧克隆原对分次放疗结果至关重要。在每日5至20次剂量期间，这种生长缓慢的肿瘤中再增殖不明显。
