Frequency of radiation-induced micronuclei in neuronal cells does not correlate with clonogenic survival.
It is generally assumed that radiation-induced micronuclei (MN) in cytokinesis-blocked cells are an expression of cellular radiosensitivity. Therefore, radiosensitive cells should have a high frequency of MN and radioresistant cells should show lower levels. We have irradiated cells of a panel of 13 neuronal cell lines of widely differing radiosensitivity [human neuroblastomas: N2alpha, SHSY5Y, SK-N-SH, KELLY and SK-N-BE(2c); murine neuroblastomas: OP-6 and OP-27; human glioblastomas: G120, G60, G28, G112, G44 and G62] and compared their radiation response using the micronucleus and standard clonogenic assays. It was found that micronucleus frequency was much higher in some of the radioresistant cell lines (N2alpha, G28, G120 and G44; SF2 >/= 0.60). These cell lines showed a high frequency of more than 0.32 MN per gray of (60)Co gamma radiation per binucleated cell. On the other hand, the more radiosensitive cell lines (OP-27 and SK-N-SH, SF2 </= 0.27) produced 0.08 +/- 0.01 and 0.04 +/- 0.01 MN per gray, respectively. OP-6, SK-N-BE(2c), G112, G62, G60 and KELLY cells constituted an intermediate group and displayed a micronucleus formation index between 0.10 and 0.24 MN per gray per binucleated cell. SHSY5Y cells showed no detectable formation of MN. In two groups [OP-6, SK-N-BE(2c), G112, G62, N2alpha and G28 or G120, G60, OP-27 and SK-N-SH], the more resistant cell lines produced more MN per unit dose. Another group [OP-6, SK-N-BE(2c), G112, G62, G44 and G120] showed no correlation between micronucleus formation and radiosensitivity. We conclude that the relationship between cell survival and micronucleus formation is not straightforward and that it would be simplistic to translate micronucleus frequency into radiosensitivity.
Akudugu
J M
JM
Department of Radiation Oncology, Faculty of Medicine, University of Stellenbosch, Tygerberg 7505, South Africa.
Slabbert
J P
JP
Serafin
A
A
Bohm
L
L
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects*; D003114:Colony-Forming Units Assay; D004247:DNA / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000473:pathology*; D015162:Micronucleus Tests; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*
D004247:DNA