MICRONUCLEI AND CLONOGENICITY FOLLOWING LOW-DOSE-RATE AND HIGH-DOSE-RATE GAMMA-IRRADIATION OF NORMAL HUMAN FIBROBLASTS

Plateau-phase human fibroblasts were irradiated at either low dose rate (Δ0.6 Gy/h) or high dose rate (78 Gy/h) with γ 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 low-dose-rate responsiveness of the short-term micronucleus assay as an indicator of the initial slope of the acute-rate survival curve.