COMPARATIVE CHANGES IN RADIOSENSITIVITY BETWEEN BONE MARROW AND A RAT TUMOR IRRADIATED UNDER ANOXIA.

Abstract

The protective effect of low oxygen concentrations in the radiosensitivity of cells has been well established by numerous experiments both in vitro and in vivo (1, 4, 5, 12). Because some tumors probably contain areas of relative hypoxia or anoxia (10), there is a possibility of variation in radiosensitivity within the tumor volume, depending on the state of oxygenation of its individual cells. One way to eliminate this variation would be to remove all oxygen, thereby equalizing the radiosensitivity of all tumor cells as far as the oxygen effect is concerned. At the same time, the surrounding normal tissues would be rendered anoxic. The question to be determined is whether or not induced anoxia would protect tumor and normal tissues to the same degree; if so, nothing has been gained. If anoxia, however, protects the normal tissue to a greater degree, than the tumor, the net effect would be a relative increase in tumor radiosensitivity. The present experiment was carried out to test this hypothesis. The data demonstrate that anoxia has a greater radioprotective effect on a normal tissue (bone marrow) than on a tumor. Materials and Methods The experimental plan was to give radiation to the lower extremities of rats bearing tumor in both legs, while the vascular supply to the left lower extremity was temporarily occluded to render it anoxic. The radiosensitivities of the femoral bone marrow and tumor in the right leg (normally oxygenated) and left leg (anoxic) were measured by determining the duration of depression of DNA synthesis in these tissues. Animals and Tumor: Male CFN rats raised in our laboratory and weighing between 150 and 300 gm. were employed. The tumor was the Walker carcinosarcoma-256. When the tumors attained a diameter of 2 to 4 cm., the animals were anesthetized with intraperitoneal sodium pentothal (50 mg./kg.), and a laparotomy was performed. The left common iliac artery was dissected free from the vein, and an arterial clamp was applied. The laparotomy incision was partially sutured, and, after waiting fifteen to twenty minutes for the left leg to become anoxic, the animals were irradiated. The clamp was always released one hour after its application; the abdominal incision was then completely closed and the animals were returned to their cages. Irradiation: The anesthetized rats were given radiation in a specially made plastic cage and positioned under a cesium-137 teletherapy machine. A collimator formed a 6 × 6-cm. square field which covered the lower extremities, but part of the pelvis was also included in the radiation field. The source-to-top-of-cage distance was 9.5 cm. Halfway during irradiation the animals were turned over to equalize the tissue dose as much as possible. Measurements made in a water-filled phantom cage indicated that the tissue dose at the mid-plane of the irradiated part of the animal was 15 per cent lower than the surface dose, and in this report all doses are expressed as midplane.