Prediction of dose response for radiation induced exchange aberrations taking cell cycle delays into account

Chromosomal aberrations (CAs) are regarded as one of the most sensitive biological indicators of genetic alterations. The aberration frequency is routinely determined in the first metaphase. Yet, the data interpretation can be complicated due to radiation induced mitotic delays. To investigate the effect of delays on CA frequency in the first mitosis, human lymphocytes were irradiated with X rays and Giemsa detectable CAs were measured at different sampling times. Besides, a computer simulation was performed reproducing the main effects under investigation, that is, CA induction and cell progression through the mitotic cycle. The CA formation model takes into account the structural organisation of interphase chromosomes in a lymphocyte nucleus, DNA double-strand break (DSB) induction and their rejoining/misrejoining. Lymphocyte transition through the cell cycle was simulated by a Monte Carlo technique. The delay was proposed to result from DNA DSBs. The predicted ratios of first/second/third cycle metaphases agree with the experimental data for control and irradiated samples. Both experimental and calculated CA frequencies in the first mitosis were nearly time-independent. This was proposed to result from de-synchronisation of the lymphocyte population.