Lack of a correlation between micronucleus formation and radiosensitivity in established and primary cultures of human tumours.
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.
Villa
R
R
Department of Experimental Oncology C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Zaffaroni
N
N
Gornati
D
D
Costa
A
A
Silvestrini
R
R
D002277:Carcinoma / Q000473:pathology; D002470:Cell Survival / Q000528:radiation effects; D002999:Clone Cells; D003571:Cytochalasin B / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000473:pathology; D015162:Micronucleus Tests / Q000592:standards*; D010051:Ovarian Neoplasms / Q000473:pathology; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
D004273:DNA, Neoplasm; D003571:Cytochalasin B