The aim of this study was to evaluate the DNA damage induced by low and high linear energy transfer radiation in two related cell lines with different radiation sensitivity, CHO10B2 and irs-20 cells (defective in DNA-PKcs). Double-strand breaks were assessed by the detection of phosphorylated histone H2AX foci (γH2AX). The number of foci increased as a function of dose for both cell lines and types of radiation. However, irs-20 cells showed a higher number of foci than the parental CHO10B2. An increase in the foci size was observed for both cell lines after lithium irradiation. This could be attributed to clusters of DNA damage. Moreover, the number of lithium-induced larger foci per nuclei increased with dose and fitted with the expected number of hits per nucleus. Concluding, γH2AX foci size provides a potential tool to characterise the intrinsic radiosensitivity of cells related to DNA damage and to compare the effects of different quality radiations.