CORRELATION OF MICRONUCLEUS AND APOPTOSIS ASSAYS WITH REPRODUCTIVE CELL-DEATH

The relationship between ionizing radiation-induced cell killing and D NA damage measured by the micronucleus and apoptosis assays was determ ined in three established cell lines (L929, HL-60, and Chang). Irradia tion experiments revealed a dose-dependent increase of micronucleated cells until a certain dose was reached. Above this dose no further inc rease of the micronucleus frequency was observed, but in HL-60 and Cha ng cells additional DNA fragmentation was detected by morphological cr iteria, characteristic of apoptosis. This change was detected at diffe rent doses for the three cell lines examined, suggesting the existence of a cell-type-dependent upper limit for the employment of the micron ucleus assay. However, the sum of both kinds of cellular DNA damage (e .g. micronucleation and morphological-like apoptosis) led to a signifi cant cell-type-independent correlation with cell survival, even above the dose where micronuclei levels saturated. Therefore, a total cell d amage 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, especi ally in conditions when apoptosis (-like) processes may occur.