The repairability during G(1) of DNA lesions eliciting sister chromatid exchanges (SCE) induced by methylmethanesulfonate (MMS) and ethylmethanesulfonate (EMS) in BrdU-substituted and unsubstituted DNA strands was determined in murine salivary gland cells in vivo. The SCE frequency was determined after exposure to MMS or EMS during early and late G(1) in the first or second cell division. The inducibility and repairability of SCE-eliciting lesions during G(1) in BrdU-substituted and unsubstituted strands were estimated considering that in the first division induction occurs on the unsubstituted strand and during the second division in one unsubstituted and one BrdU- substituted DNA strand. The results indicate that DNA lesions induced by MMS are 50% repaired in both the BrdU-substituted and unsubstituted strands and those induced by EMS are 60% repaired in the unsubstituted strand but only 20% in the BrdU-substituted strand. The increase in sensitivity of the BrdU-substituted strand to SCE induction with respect to the unsubstituted strand was 155 and 45% for MMS and EMS, respectively. These results imply that SCE-inducing lesions produced by MMS and EMS are only partially repaired and that BrdU incorporation could sensitize DNA not only to the induction of lesions eliciting SCE, but also to the induction of non-repairable lesions.

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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.

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