Different behavior of SCE-eliciting lesions induced by low and high doses of busulfan

Our previous studies suggested a dose-dependent transition in the types of DNA lesions induced by busulfan, as measured using the comet assay and by micronuclei analyses. The aim of the present study was to investigate the dose-dependent induction of different sister-chromatid exchange-eliciting lesions; lesions were distinguished by their efficiency in producing sister-chromatid exchange (SCE), and by their reparability during G1. Synchronously dividing murine salivary gland cells were assayed in vivo. Groups of mice were intraperitoneally injected with either 30 or 80 micromol busulfan/kg body weight solution at early or late G1. The rate of SCE/micromol busulfan/kg body weight obtained by exposure at late G1 with the high dose was twice that of the low dose. SCE induction during early G1 was higher than at late G1 with both doses; only the low-dose response was statistically significant. The frequency distribution of SCEs per cell demonstrated that cells exposed at the late G1 phase showed typical profiles that closely fit a Gaussian curve. However, an irregular profile was obtained for cells treated during early G1, which showed some cells with high-SCE frequency. Cells treated in early G1 have more time to repair lesions before DNA synthesis; therefore, the results suggest that instead of repair, secondary SCE-eliciting lesions during G1 were produced, especially at the lower dose. The results obtained in this study indicate that there are dose-dependent differences in the types of SCE-eliciting lesions induced by busulfan.