Estimation of the Initial Slope of the Cell Survival Curve after Irradiation from Micronucleus Frequency in Cytokinesis-Blocked Cells

We have already reported that the α/β ratio of the cell survival curve could be estimated from the micronucleus frequency in cytokinesis-blocked cells treated with cytochalasin-B after irradiation. In this paper, we investigate the direct relationship between the α value and the appearance of micronuclei. Cells of the SCCVII, RIF-1, EMT6, V-79, CHO, HeLa and human esophageal cancer cell lines were used for the study. Low-dose-rate irradiation was used to determine the α component of the relationship between dose and micronucleus frequency according to the linear-quadratic (LQ) model. A reduction of the dose rate from 3.09 to 0.0142 Gy/min correspondingly decreased the micronucleus frequency; however, the fraction of binucleate cells without micronuclei was not affected in SCCVII and RIF-1 cells. When this fraction was defined as the normal nuclear division fraction, it decreased exponentially as a function of radiation dose. Then dose vs normal nuclear division fraction (NNDF) was fitted as follows: -ln NNDF = aD + C, where D is radiation dose in grays and C is constant. The slope of the dose vs normal nuclear division fraction was not affected by dose rate. The correlation was also explored between the slope (a) and the α value of the cell survival curve determined by the colony formation assay in cells of eight cell lines. These two values showed extremely high agreement: α = 1.01a + 0.00795 (r = 0.99, P < 0.01). This assay was applied to estimate the α value of the cell survival curve of human esophageal cancer cell lines established from surgical specimens.