Influence of DNA double-strand break rejoining on clonogenic survival and micronucleus yield in human cell lines

To examine the role of DNA double-strand break (DSB) rejoining in cell survival and micronucleus yield after 60Co gamma-irradiation.

Thirteen human cell lines (six glioblastoma, five prostate, one melanoma, one squamous cell carcinoma) were irradiated with 60Co gamma-rays to doses of 0-10Gy for cell survival and micronucleus measurements and 0-100Gy for DSB rejoining. Measurements were performed using standard clonogenic, micronucleus and constant-field gel electrophoresis assays.

Radioresistance and micronucleus yield were positively correlated (r=0.74, p=0.004). A significant cell type-dependent correlation was demonstrated between total (0-20 h) DSB rejoining and cell survival (r=0.86, p=0.03 for glioblastomas; r=0.79, p=0.04 for other cell lines), with more resistant cell lines showing higher levels of DSB rejoining. No relationship was apparent between fast (0-2 h) or slow (2-20 h) DSB rejoining and clonogenic survival. While there was no relationship between total or slow DSB rejoining and micronucleus yield, a significant and cell type-specific correlation emerged between fast rejoining and micronucleus yield for the glioblastomas (r=0.89, p=0.04) and other cell lines (r=0.76, p=0.04). Cell lines with higher levels of DSB rejoining within 2 h of irradiation showed higher yields of micronuclei.

Fast DSB rejoining, possibly through interaction with slow DSB rejoining, appears to play an important role in the formation of micronuclei. However, total DSB rejoining reflects intrinsic radiosensitivity. Consideration of differences in DSB rejoining kinetics might contribute to a better understanding of the significance of cell survival and micronucleus data in the clinical and radiation protection setting.