Zätterström U K, Engellau J, Johansson M C, Wennerberg J, Kjellén E
Department of Oto-rhino-laryngology, University Hospital, Lund, Sweden.
Acta Oncol. 1995;34(2):205-11. doi: 10.3109/02841869509093957.
The effect of irradiation on S-phase duration (Ts), labelling index (LI), potential doubling time (Tpot), and cell cycle phase distributions was determined by DNA flow cytometry in xenografted human squamous cell carcinoma of the head and neck (SCCHN). Tumours were treated with a single dose of 3 Gy, and excised at intervals over a 90-h period. Six hours before each excision the tumours were labelled in vivo with bromodeoxyuridine (BrdUrd). Although the growth rate of irradiated tumours was comparable with that of untreated controls, analysis of BrdUrd uptake revealed a transient reduction of LI and a prolongation of Ts in irradiated tumours. Maximum mean Tpot was 931 days in irradiated tumours as compared to 13 days in untreated controls. The variations in Ts, LI and Tpot all occurred within the first hours after irradiation; during the remainder of the observation time, the values of the variables did not differ from those of untreated controls. In irradiated tumours the distribution of cells according to DNA content changed significantly on three occasions during the observation period: 1) Parallel to the initial lowering of LI and prolongation of Ts there was a transient increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S and G2; 2) At 18 h, the most pronounced cell cycle phase redistribution occurred when the G0/G1 fraction decreased and the S and G2 phase fractions increased; 3) At 66 h (i.e., approximately one cell cycle later), the pattern was the same as that after 18 h. The findings suggest that the transient prolongation of DNA replication seen in SCCHN cells immediately after a single radiation dose is a symptom of DNA damage inflicted during late G1 or early S-phase, and that this disturbance in DNA synthesis is associated with the subsequent accumulation of cells in G2 phase.
通过DNA流式细胞术测定了照射对异种移植的人头颈鳞状细胞癌（SCCHN）的S期持续时间（Ts）、标记指数（LI）、潜在倍增时间（Tpot）和细胞周期阶段分布的影响。肿瘤接受单次3 Gy剂量的治疗，并在90小时内每隔一段时间切除。每次切除前6小时，用溴脱氧尿苷（BrdUrd）对肿瘤进行体内标记。尽管照射后肿瘤的生长速率与未治疗的对照组相当，但对BrdUrd摄取的分析显示，照射后肿瘤的LI短暂降低，Ts延长。照射后肿瘤的最大平均Tpot为931天，而未治疗的对照组为13天。Ts、LI和Tpot的变化均发生在照射后的最初几小时内；在观察期的其余时间里，这些变量的值与未治疗的对照组没有差异。在照射后的肿瘤中，观察期内细胞DNA含量分布在三个时间点发生了显著变化：1）与LI的初始降低和Ts的延长同时，G0/G1期细胞比例短暂增加，S期和G2期细胞比例减少；2）在18小时时，最明显的细胞周期阶段重新分布发生，此时G0/G1期细胞比例降低，S期和G2期细胞比例增加；3）在66小时（即大约一个细胞周期后），模式与18小时后相同。这些发现表明，单次辐射剂量后SCCHN细胞中立即出现的DNA复制短暂延长是G1晚期或S期早期造成的DNA损伤的一种表现，并且这种DNA合成的干扰与随后G2期细胞的积累有关。
