Correlation of micronucleus and apoptosis assays with reproductive cell death.

The relationship between ionizing radiation-induced cell killing and DNA damage measured by the micronucleus and apoptosis assays was determined in three established cell lines (L929, HL-60, and Chang). Irradiation experiments revealed a dose-dependent increase of micronucleated cells until a certain dose was reached. Above this dose no further increase of the micronucleus frequency was observed, but in HL-60 and Chang cells additional DNA fragmentation was detected by morphological criteria, characteristic of apoptosis. This change was detected at different doses for the three cell lines examined, suggesting the existence of a cell-type-dependent upper limit for the employment of the micronucleus assay. However, the sum of both kinds of cellular DNA damage (e.g. micronucleation and morphological-like apoptosis) led to a significant cell-type-independent correlation with cell survival, even above the dose where micronuclei levels saturated. Therefore, a total cell damage assay, involving the inclusion of micronuclei and morphological-like apoptotic events, should be considered when evaluating the use of a predictor assay for ionizing radiation-induced cell killing, especially in conditions when apoptosis (-like) processes may occur.