Chromosomal Aberrations Induced by Plasma from Irradiated Patients: An Indirect Effect of X Radiation

This is the authors' abstract. We don't add key points for this paper.

Ionizing radiations produce distinct chromosomal aberrations in human cells exposed either in vitro or in vivo (1, 2). Although chromosome breakage is generally thought to result from ionizations of the directly exposed chromosomes (3), the secondary effects of radiation might also induce chromosome lesions in irradiated cells. Experiments conducted in this laboratory to test for an indirect effect of x rays on chromosome integrity (4, 5) showed that cell-free plasma from patients who had received large doses of therapeutic x radiation could break chromosomes of nonirradiated leukocytes. The present paper extends the observations of the effects of the “plasma breakage factor” on leukocyte chromosomes and summarizes data on breakage frequencies in a control population. Subjects Twelve patients who were receiving or scheduled for therapy for solid tumors were chosen as experimental subjects. X-ray tumor doses ranged from 1,000 to 7,000 R. None of the patients received radiomimetic drugs, and none had clinical symptoms of viral infections. The tumors being irradiated were variable, both in location and in cell type (Table I). Eleven of the 12 patients studied were men. Eleven were treated with a 2 MeV van de Graaff generator, h.v.l. 8 mm Pb, FSD 100 cm. One patient (Case III) was treated with a superficial therapy machine, h.v.l. 3.4 mm Al, FSD 30 cm. For controls, 14 hospital employees (10 women and 4 men) were chosen. X-ray exposure of 13 controls was negligible, consisting of occasional chest roentgenograms. The other control had a gastrointestinal series during the experiment, but there was no significant increase in chromosome breakage in cultures of her cells and plasma one week after exposure to the diagnostic radiation, compared with two cultures taken before the exposure. None of the controls had symptoms of viral infection when the blood was collected. Studies were carried out on three-day leukocyte cultures containing the following combinations of cells and plasma: (a) leukocytes from nonirradiated control subjects + autologous plasma (Normal Cells/Autologous Plasma); (b) leukocytes from nonirradiated control subjects + plasma from a second control (Normal Cells/Homologous Normal Plasma); (c) leukocytes from control subjects + plasma from nonirradiated tumor patients (Normal Cells/Pretreatment Patient Plasma); (d) leukocytes from nonirradiated controls + plasma from irradiated tumor patients (Normal Cells/Patient Plasma); (e) leukocytes from irradiated tumor patients + autologous plasma (Patient Cells/Patient Plasma), and (f) leukocytes from irradiated tumor patients + plasma from nonirradiated controls (Patient Cells/Normal Plasma). Peripheral blood leukocytes were cultured by a previously described modification (5) of the technic of Moorhead et al. (6), and aberrations were classified, using the following criteria. Small achromatic lesions in a single chromatid were scored as chromatid gaps.