Micronuclei and clonogenicity following low- and high-dose-rate gamma irradiation of normal human fibroblasts.

Plateau-phase human fibroblasts were irradiated at either low dose rate (approximately 0.6 Gy/h) or high dose rate (78 Gy/h) with gamma rays and then released from contact inhibition. The frequency of cells containing micronuclei monitored at daily intervals showed that induction was dependent on both dose and dose rate with a peak incidence at 3 days postirradiation. Cumulative frequency distributions indicated a reduction by a factor of 4 when the dose was delivered chronically as opposed to acutely. Distributions also suggested that micronuclei-containing cells persist over days, while the dose responses (different by a factor of 2.8) for both high and low dose rate indicated a plateau, particularly following higher doses at low dose rate. Data were not consistent with this response being due to cell cycle delay. Delayed plating resulted in both a reduced incidence of cells with micronuclei and enhanced survival following high- but not low-dose-rate irradiation, with the response being complete by 6 h. Cell surviving fraction and the fraction of cells with micronuclei were negatively correlated, but the relationships were different between the high- and low-dose-rate irradiations. This divergence mitigates against using low-dose-rate responsiveness of the short-term micronucleus assay as an indicator of the initial slope of the acute dose-rate survival curve.