Bergs J W J, Franken N A P, ten Cate R, van Bree C, Haveman J
Academic Medical Center, University of Amsterdam, Department of Radiotherapy, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Mutat Res. 2006 Feb 22;594(1-2):148-54. doi: 10.1016/j.mrfmmm.2005.08.002. Epub 2005 Sep 30.
Cisplatin was found to radiosensitize SW-1573 cells by inhibition of PLDR. Therefore, it was investigated whether cisplatin combined with gamma-radiation leads to an increase in the number of chromosomal aberrations or apoptotic cells compared with radiation alone.
Confluent cultures of the human lung carcinoma cell line SW-1573 were treated with 1 microM cisplatin for 1 h, 4 Gy gamma-radiation, or a combination of both. Cell survival was studied by the clonogenic assay. Aberrations were analysed by FISH in prematurely condensed chromosomes (PCC) and the induction of apoptosis by counting fragmented nuclei.
A radiosensitizing effect of cisplatin on cell survival was observed if time for PLDR was allowed. An increased number of chromosomal fragments were observed immediately after irradiation compared with 24 h after irradiation whereas color junctions are only formed 24 h after irradiation. No increase in chromosomal aberrations was found after combined treatment, but a significantly enhanced number of fragmented nuclei were observed when confluent cultures were replated after allowing PLDR.
The inhibition of PLDR by cisplatin in delayed plated SW-1573 cells did not increase chromosomal aberrations, but increased the induction of apoptosis.
发现顺铂通过抑制PLDR使SW - 1573细胞对辐射敏感。因此,研究了与单独放疗相比,顺铂联合γ射线辐射是否会导致染色体畸变或凋亡细胞数量增加。
用人肺癌细胞系SW - 1573的汇合培养物分别用1 microM顺铂处理1小时、4 Gy γ射线辐射或两者联合处理。通过克隆形成试验研究细胞存活情况。通过FISH分析早熟凝集染色体(PCC)中的畸变情况,并通过计数碎片化核来分析凋亡诱导情况。
如果给予PLDR时间,观察到顺铂对细胞存活有放射增敏作用。与照射后24小时相比,照射后立即观察到染色体片段数量增加,而颜色连接仅在照射后24小时形成。联合处理后未发现染色体畸变增加,但在给予PLDR后对汇合培养物进行再接种时,观察到碎片化核的数量显著增加。
顺铂对延迟接种的SW - 1573细胞中PLDR的抑制并未增加染色体畸变,但增加了凋亡诱导。