We studied the dose response of pulmonary changes at 3 weeks after 1-25 Gy irradiation and we investigated the effects of an anti-inflammatory drug. Wistar rats were given a single dose of 1-25Gy irradiation to the thorax. Group one was treated with saline only, while group two was administered subcutaneously a combination of pentoxifylline (35 mg/kg) and dexamethasone (1 mg/kg) twice per week. Lungs were examined histochemically and number of neutrophile granulocytes, alveolar septal thickness, air/tissue ratio, number of alveoli per field, number of type II pneumocytes per alveolus, and occludin 1 expression were measured. A significant dose-dependent depletion of type II pneumocytes was found after irradiation with a dose of 1 Gy and higher. Alveolar neutrophils increased after 1 Gy with a dose dependency noted after 10-25Gy and alveolar septa thickening followed 5-25 Gy. A lower occludin 1 expression was observed in animals irradiated with the doses of 5 20 Gy, indicating an effect on vascular permeability. Anti-inflammatory therapy partially inhibited the increase of neutrophils at all radiation doses and the depletion of type II pneumocytes after doses of 1, 10, and 15 Gy. Occludin 1 did not decrease in the lungs of rats treated with the anti-inflammatory drugs as it did in most rats treated only with saline. Our results suggest that pneumocytes depletion is a major factor responsible for radiation pneumonitis development and that these changes may be compensated for provided radiation doses are below the threshold.

Department of Radiobiology Purkyne Military Medical Academy Trebesska 1575 Hradec Králoré 50001 Czech Republic

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