Factors influencing chromosome aberration yields in the human peripheral leukocyte system

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The culture procedure for peripheral leukocyte tissue has been considered a simple, unique method for studying radiation-induced chromosome aberrations. Cells that can be stimulated to undergo transformation and cell division in culture were thought to constitute a population of uniform radiosensitivity. It was thus believed that as long as the investigator took the precaution to fix leukocyte cultures at a time that precluded the possibility of obtaining any cells in their second division in culture, the system would provide uniform quantitative estimates of radiation-induced chromosome aberration yields. Experiments described in this paper suggest that these assumptions are erroneous. Successive samples of colchicine-metaphase chromosome preparations from the same culture indicate that with increasing time in culture, the aberration yield gradually rises to a peak, drops off, and then a second peak occurs later. The data also show the peak yield of aberrations occurring at a time when there is a significant frequency of cells in their second division in culture, as measured by either loss of acentric fragments or segregation of tritiated-thymidine label. This suggests the existence of two subpopulations of cells with differing radiosensitivities and rates of progression through the process of transformation to cell division. Regression analysis of the dose-response curves of the two-break aberrations shows that most of them result from two independent ionizing events. This is in accord with earlier work on the human leukocyte system and other cytological system but differs from that of Evans 16–20.