An Ultrastructural Study of the Development of Radiation Injury in the Lung

The lung represents a dose-limiting structure in the radiation treatment of thoracic and chest wall lesions. It also contains one of the richest capillary networks in the body. Thus, radiation-induced changes noted within the lung indicate reaction of small vessels in other tissues. A better understanding of the nature of radiation damage in the lung could lead to the development of improved technics or modifications. These in turn would allow higher doses of radiation to the lung, without subsequent severe injury. Changes in the lung after therapeutic and experimental doses of radiation have been described in several extensive reports (3, 4, 9). Of the experimental studies on radiation pneumonitis, that of Jennings and Arden (3) is one of the more recent. These investigations were limited by the resolution of the light microscope, which did not allow visualization of the detailed structure of the alveolar capillary wall. Neither did it permit accurate identification of the cell types involved in reaction to injury. Detailed examination of the various components of the alveolar capillary wall was believed possible with use of the electron microscope. With this instrument, the specific cells involved in the reaction to radiation and in repair of injury could be studied. Also, detailed study of the structure of the repaired lung would be possible. Materials and Methods Twenty-five male Sprague-Dawley rats from the specific pathogen-free colony of the United States Naval Radiological Defense Laboratory were employed. The rats were four months of age and free of any pulmonary infections. Irradiation was administered through a left anterior chest field of 5 × 2.5 cm, using 250 kVp radiation with a h.v.l. of 1.28 mm Cu. The animals were anesthetized with Nembutal for the irradiation, and their bodies shielded with lead of one-fourth-inch thickness. The irradiated volume included the left lung and mediastinum, but not the right lung. A dose of 2,000 rads was delivered to the mid-plane of the left chest. Animals were killed at various periods, ranging from one hour to twelve months after irradiation. Control animals were taken at random from each group, and their lungs were prepared in a manner similar to that used in the irradiated animals. For removal of the specimens, ether anesthesia was employed and the left hemi-thorax was opened rapidly. While the animal was still breathing, a small portion of the peripheral zone of the left upper lobe was removed. This specimen was quickly minced in a solution of 1 per cent osmium tetroxide, buffered with Veronal acetate containing sucrose, according to the method of Caulfield (1). The tissues were fixed for one hour at room temperature and then embedded in Araldite, as described by Luft (7).