Lack of a correlation between micronucleus formation and radiosensitivity in established and primary cultures of human tumours

Summary 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. The standard assay for radiosensitivity has been for some time the in vitro measurement of clonogenic cell survival, and the surviving fraction at 2 Gy (SF2) is still currently inves-tigated as an indicator of clinical tumour radioresponsivenes