单次大剂量照射对Lewis肺癌移植瘤的放射生物学效应

The Bio-effects of High Single-dose Radiation on Xenografts of Lewis Lung Carcinoma

目的研究同等生物有效剂量（biological effective dose，BED）下，单次大剂量照射对Lewis肺癌移植瘤的生物学作用。方法构建Lewis肺癌C57小鼠移植瘤模型，待移植瘤直径达4～6mm时随机分为3组：空白对照组（OGy组）、单次大剂量组（12Gy／1 f／1d组）及常规照射组（22Gy／11f／15d组），后两组BED值均为26．4Gy。绘制移植瘤生长曲线，于第1次照射后的第1、3、8、15、21d处死荷瘤小鼠，收集肿瘤组织并采用流式细胞术、免疫荧光等实验技术检测肿瘤细胞的乏氧、损伤及周期的变化。结果两种剂量分割模式均可抑制小鼠移植瘤的生长，单次大剂量组肿瘤生长抑制更为明显（P％0．05）。单次大剂量组首次照射后第3、8、15d乏氧细胞较常规照射组低（P％0．05），且其第1、3d磷酸化组蛋白（7-H2AX）阳性肿瘤细胞数高于后者（P〈O．05）。两种剂量分割模式可使G0／G1期细胞比例减少，G2／M期细胞比例增加，且单次大剂量组G2／M期细胞增加更为明显（P〈0．05）。结论同等BED不同分割模式下，单次大剂量放射治疗较常规分割放射治疗对肿瘤的生长抑制作用更为显著，基于线性二次模型（LQ模型）的BED可能低估了大分割放疗的生物学效应。

Objective To investigate the bio-effects of high single-dose radiation on xenografts of Lewis lung carcinoma. Methods Female 8-week-old C57 mice bearing 4-6 mm diameter I.ewis lung carcinoma tumors in the hind legs were divided into 3 groups, control group （0 Gy）, high single-dose group （12 Gy/one fraction/day） and routine radiation group （22 Gy/ll fraction/15 d）. The mean biological effective dose （BED） of both radiation groups was 26.4 Gy. Changes in hypoxia, DNA damage and cell cycle of the tumor cells at 1, 3, 8, 15 and 21 d after first irradiation was assessed by immunofluorescence and flow-cytometry and the tumor growth curve was also made. Results Compared to the fractionated treatment, the tumor growth was delayed after single dose irradiation. The percent of hypoxic cells after single dose radiation was lower than fractioned irradiation at 3, 8, 15 d after first radiation. The loci of y-H2AX showed that the single dose caused heavier DNA damages than fractioned irradiation at 1, 3 d after first radiation. The decline of G0/GI percentage and increase of G2/M percentage of cells was found in both radiation schedules, but the Gz/M percentage after single dose radiation was higher. Conclusion In the C57 mice bearing Lewis lung carcinoma, the high single-dose regimen inhibits the tumor growth more than fractioned irradiation. We hypothesized that conversion of high single-dose to BED using the LQ formalism under estimated the in vivo effect of hypofractionated radiation.