NEWER ASPECTS IN CELLULAR RADIOSENSITIVITY.

Abstract

Why cells differ in their response to ionizing radiation is a recurrent question among investigators in the field of radiobiology, stressed again in two recent review papers (1, 2). The results herein reported seem to shed light on this query. For a number of years the author's interest has been focused mainly on the unraveling of the factor(s) involved in differential cellular radiosensitivity. This interest evolved from her earliest experiments which demonstrated that when mixed cells of tissues, such as kidneys, tongue, and heart, were exposed in vitro to ionizing radiation (x-rays or radium), the lymphocytes, granulocytes, macrophages, and fibroblasts were gradually destroyed by increased radiation doses, whereas the epithelial cells continued to proliferate (3). Subsequent experiments demonstrated a difference in radiosensitivity between two analogous mammary tumors (4). In the hope of elucidating this phenomenon, experiments were directed toward the detection of intrinsic properties of specific cell types which might be responsible for differential cellular radiosensitivity. Specifically, experiments in the Cancer and Radiobiological Research Laboratory, New York, N. Y., have been concerned with the detection of a possible relationship between cellular structure, function, and radiosensitivity. While similar investigations had previously been carried out at cellular levels (5, 6), the recent studies were performed at a subcellular level. Modern technics, such as electron microscopy which permits the visualization of cellular ultrastructures, and ultracentrifugation procedures which facilitate the separation and isolation of the major intracellular components, were employed. Previous investigations were concerned with changes induced by irradiation in the nuclear material; the recent studies were focused on the changes taking place in the cytoplasmic ultrastructures. Observations to date are briefly presented as a review record of this new phase of research. Material and Methods The experimental material in the present studies consisted of two malignant tumors, one a slowly growing epithelial and the other a rapidly growing spindle-cell type. They were of the same genetic origin, and both were propagated in isologous parent hosts of the same inbred strain of mice (DBA/212). Thus, the material constituted an ideal model system for studying the properties of two different malignant cell types where the possible influence of heterologous host factors was avoided. Lymph nodes of whole-body irradiated mice and of control nonirradiated mice were employed for comparative purposes. A General Electric Maximar x-ray machine operating at 200 kv, 15 ma, was employed for radiation purposes. The incident beam was filtered through 0.5 mm Cu and 1.0 mm Al.