Villa R, Zaffaroni N, Gornati D, Costa A, Silvestrini R
Department of Experimental Oncology C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Br J Cancer. 1994 Dec;70(6):1112-7. doi: 10.1038/bjc.1994.457.
The radiation-induced genotoxic damage in three established cell lines and 15 primary cultures of human malignant melanoma and ovarian carcinoma showing different radiosensitivity was tested by the cytokinesis-block micronucleus assay. A dose-related increase in micronucleus frequency was observed in all the cell systems. The mean number of micronuclei per Gy of ionising radiation per binucleated cell was respectively 0.44 +/- 0.0075 and 0.43 +/- 0.04 for M14 and JR8 malignant melanoma cell lines and 0.19 +/- 0.013 for the A2780 ovarian cancer cell line. The number of micronuclei did not rank the cell lines in the same order of radiosensitivity as clonogenic cell survival, which showed a surviving fraction at 2 Gy of 0.38 +/- 0.02 for JR8, 0.34 +/- 0.05 for M14 and 0.22 +/- 0.007 for A2780. As regards primary tumour cultures, no correlation was observed between micronucleus induction and surviving fraction at 2 Gy. In conclusion, the discrepancy we observed between micronucleus formation and cell death raises doubts about the potential of the micronucleus assay as a preclinical means to predict radiosensitivity.
采用胞质分裂阻滞微核试验，检测了三种已建立的细胞系以及15种人恶性黑色素瘤和卵巢癌原代培养物中的辐射诱导遗传毒性损伤，这些细胞系和原代培养物表现出不同的放射敏感性。在所有细胞系统中均观察到微核频率呈剂量相关增加。对于M14和JR8恶性黑色素瘤细胞系，每个双核细胞每戈瑞电离辐射的微核平均数分别为0.44±0.0075和0.43±0.04，对于A2780卵巢癌细胞系为0.19±0.013。微核数量对细胞系放射敏感性的排序与克隆形成细胞存活情况不同，克隆形成细胞存活情况显示，JR8在2 Gy时的存活分数为0.38±0.02，M14为0.34±0.05，A2780为0.22±0.007。对于原代肿瘤培养物，在2 Gy时微核诱导与存活分数之间未观察到相关性。总之，我们观察到的微核形成与细胞死亡之间的差异，让人对微核试验作为预测放射敏感性临床前手段的潜力产生怀疑。
