Fechner G, Perabo F G E, Schmidt D H, Haase L, Ludwig E, Schueller H, Blatter J, Mller S C, Albers P
Department of Urology, Bonn University, Bonn, Germany.
Urology. 2003 Feb;61(2):468-73. doi: 10.1016/s0090-4295(02)02156-8.
Despite clinical use, the radiosensitizing effect of gemcitabine (2'2'-difluorodeoxycytidine) in human transitional cell carcinoma (TCC) has not been shown to date. We investigated gemcitabine as a radiosensitizer for human TCC cells.
Monolayer cultures of RT112 (G1, p53 wild type), RT4 (G1-G2, p53 wild type), T24 (G3, p53, mutant type), and SUP (G4, p53 mutant type) cells were incubated in medium with gemcitabine. Electron beam radiation was applied alone, simultaneous, or 3, 6, 12, and 24 hours after gemcitabine. Jurkat leukemia cells were used as controls for radiation toxicity. Cell survival was determined 6, 12, 24, 48, and 72 hours after radiation by microculture tetrazolium assay. DNA damage was evaluated by flow cytometric assessment of poly(ADP-ribose) polymerase, and apoptosis was determined by terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling and flow cytometric assessment after annexin-V and propidium iodide labeling.
In all TCC cell lines, radiation alone caused only little and insignificant growth inhibitory effects at 10 Gy. Gemcitabine alone had a dose-dependent cytotoxic and apoptosis inducing effect on all TCC cell lines independent of p53 status. Assays combining radiation with gemcitabine in different dose and time schedules demonstrated no radiosensitizing effect in TCC cells.
Gemcitabine is effective in TCC cell lines independent of p53 status. A radiosensitizing effect could not be demonstrated. Again, p53 status was not predictive of the radioresponse in the bladder cancer cell lines. Clinical studies with gemcitabine and radiotherapy might nevertheless yield different results but should be performed with utmost caution.
尽管吉西他滨（2'2'-二氟脱氧胞苷）已在临床上使用，但其对人移行细胞癌（TCC）的放射增敏作用迄今尚未得到证实。我们研究了吉西他滨作为人TCC细胞放射增敏剂的作用。
将RT112（G1期，p53野生型）、RT4（G1-G2期，p53野生型）、T24（G3期，p53突变型）和SUP（G4期，p53突变型）细胞的单层培养物置于含有吉西他滨的培养基中孵育。单独施加电子束辐射，或在吉西他滨处理后同时、3、6、12和24小时施加辐射。将Jurkat白血病细胞用作辐射毒性的对照。通过微量培养四唑盐试验在辐射后6、12、24、48和72小时测定细胞存活率。通过聚（ADP-核糖）聚合酶的流式细胞术评估来评价DNA损伤，并通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记以及膜联蛋白-V和碘化丙啶标记后的流式细胞术评估来确定细胞凋亡。
在所有TCC细胞系中，单独辐射在10 Gy时仅引起微小且不显著的生长抑制作用。单独使用吉西他滨对所有TCC细胞系具有剂量依赖性的细胞毒性和凋亡诱导作用，且与p53状态无关。将辐射与吉西他滨以不同剂量和时间方案联合进行的试验表明，在TCC细胞中未显示出放射增敏作用。
吉西他滨对TCC细胞系有效，且与p53状态无关。未证实其具有放射增敏作用。同样，p53状态不能预测膀胱癌细胞系的放射反应。不过，吉西他滨与放疗的临床研究可能会产生不同结果，但应极其谨慎地进行。
