Radiation breakage of human chromosomes in vivo and in vitro.

Abstract

Chromosomes in the leukocytes from the peripheral blood constitute an almost ideal biological dosimeter: they are readily available for study, they show damage immediately following irradiation, and they also may show radiation changes years after the exposure of the person concerned. The immediate effects are exhibited by cells which were irradiated while circulating in the blood. Since the lifetime of the leukocytes in the blood stream is probably only a few days, the immediate effect should disappear rapidly as they are replaced by new leukocytes. This phenomenon is seen clearly in the work of Tough et al. (1), which showed the disappearance of cells exhibiting radiation damage in a matter of days from the peripheral blood of a patient who received a single dose of partial body irradiation. On the other hand, radiation injury to the precursors of the monocytes and large lymphocytes—the two kinds of leukocyte which can divide—persist probably for the lifetime of the individual. Thus irradiation to the lymphoid tissue and reticuloendothelial system, where precursors of these cells are found, should result in chromosome breakage visible years later. This is most dramatically illustrated in the studies of Bender (2), who found a high frequency of chromosome aberrations in men who had been exposed accidentally to whole-body irradiation some twenty-nine months prior to his study. In this paper we shall present some preliminary data on the immediate effect of radiation on leukocytes irradiated in vivo and in vitro. Table I shows the distribution of chromosome numbers in two patients undergoing radiation therapy. At the top are observations on leukocytes taken from a thirty-seven-year-old woman just before and immediately after she was exposed to 300 r of whole-body irradiation delivered in a single session. The increase of cells with 47 chromosomes is due to the fragmentation of the chromosomes by irradiation. The number in parentheses indicates that two of the seven cells with 46 chromosomes contained obvious radiation-induced chromosome aberrations. One of these cells is shown in Figure 1. The technic used was essentially that of Moorhead and his coworkers (3). Also shown in Table I are the results obtained in a young man during a course of therapy. The technic used was not altogether satisfactory at the time these data were obtained and some of the chromosomes were split during preparation. Nevertheless, the effect of the irradiation in widening the distribution of chromosome numbers is marked. The first post-irradiation sample was examined after a dose of 570 r to the uninvolved lymph node areas through a single 10 × 15-cm. epigastric port. We estimate that this corresponds to an average dose of about 70 r to the circulating leukocytes. As therapy proceeded and the dose increased, there was a corresponding decrease in cells with 46 chromosomes and a corresponding increase in aberrations. One of these cells is shown in Figure 1.