Micronucleus induction in 10 human tumour cells after high- and low-dose radiation

Abstract

A number of data measuring survival of animal or human cells to low LET ionizing radiation have demonstrated that these cells may be hypersensitive to doses below 1 Gy, possibly due to the absence of an inducible repair mechanism, which is observed at higher doses. The production of micronuclei (MN) in cells exposed to ionizing radiation reflects genotoxic damage. Moreover, the micronucleus assay is sensitive to low radiation doses. We have exposed 10 human tumour cell lines to doses ranging between 0.12 and 4 Gy. Using cytochalasin B to block the cells in a binucleate phase, we have scored the fraction of binucleate cells (BNC) expressing MN, as well as the number of MN per BNC, as a function of γ-ray dose. Experimental points were fitted with a binomial equation. Doses from 1 to 4 Gy were fitted separately from those below 1 Gy, and the initial slopes after both fits were compared. Taken together, the initial slopes of MN induction after low-dose (LD) irradiation were not different from those after high-dose (HD) irradiation. Only in one cell line was a significant increase in MN production detected after LD irradiation. This cell line had the shallowest linear term after HD irradiation. It appeared that the likeliness of expressing hypersensitivity at LD was correlated with the quadratic term of MN induction at HD, which does not contradict an inducible repair hypothesis. However, the failure of observation of a significant hypersensitivity at LD for nine cell lines, and the high variability of response at LD suggests that this occasional effect may be influenced by other factors as well.