방사선 폐염의 cyclophosphamide에 의한 증강효과에 관한 실험적 연구

Abstract

胸郭癌에 대한 根治的 放射線治療時 發生되는 正常肺組織의 放射線 損傷에 의한 放射線肺炎 및 纖維化가 臨床的으로 主要한 問題로 대두되어 왔다. 또한 癌患者에게 抗癌劑와 放射線照射의 倂用治療가 活用되면서 抗癌劑가 癌組織 뿐아니라 正常組織에 대한 放射線損傷을 增强시킨다는 事實이 보고되고 있으며, 특히 肺臟에서 放射線肺炎의 유발을 促進시키는 抗癌劑로 Actinomycin-D, Adriamycine, Bleomycin, Cyclophosphamide, Hydroxyurea, Vincristine 등이 주요한 藥劑로 알려져 왔다. 저자는 기니피그（Guinea Pig）의 右側肺에 放射線量 10, 20 및 30Gy 單一照射群과 Cyclophosphamid 注射를 倂行한 放射線照射群에서 유발된 放射線肺炎 및 纖維化를 放射線學的 및 病理組織學的으로 比較分析하여 다음과 같은 結論을 얻었다. 1. 放射線 照射線量이 많을수록 肺損傷의 정도가 더욱 심하였다. 2. 胸部 X-線像으로 放射線照射後 30日에 肺野에 輕微한 肺炎巢가 觀察되며 점차 病影의 範圍와 濃度가 增加하고, 無氣肺 및 纖維化에 의한 容積減少로 인한 心臟變位가 동반되었다. 3. 放射線 單一照射群에 비해 Cyclophosphamide 注射를 倂行한 放射線照射群에서 더욱 심한 放射線肺炎 및 纖維化의 放射線學的 所見이 觀察되었다. 4. 病理組織學的 變化所見은 肺胞虛脫, 炎症細胞 및 貪食細胞의 浸潤, 肺胞上皮細胞의 增殖, 肺胞中隔의 肥厚 및 纖維化이며, 점차적으로 이상의 病理組織學的 變化가 增加됨을 觀察할 수 있었다. 5. Cyclophosphamide 注射를 倂行한 放射線照射群에서는 放射線 單一照射群에 比해 膠原質纖維의 生成 및 肺胞中隔의 纖維化가 早期에 나타났고 그 정도도 심하였다. 6. Cyclophosphamide 注射를 倂行한 放射線量 20Gy 單一照射群에서의 肺胞虛脫 및 肺胞中隔의 纖維化의 정도는 放射線量 30Gy 單一照射群에서와 同一하여, Cyclophosphamide의 投與量-效果因子（dose-effect factor）가 1.5임을 알 수 있었다. 7. Cyclophosphamide 注射를 倂行한 放射線照射群에서는 放射線 單一照射群에 比해 放射線肺炎 및 纖維化가 심한 바 이는 倂用된 Cyclophosphamide에 의한 放射線損傷의 增强效果로 생각되었다. ; Radiation therapy became widely used for treatment of malignant disease during the first two decades of this century and thereafter reports of radiation pneumonitis and pulmonary fibrosis after irradiation to thorax are appearing more frequently in literature. The incidence and severity of radiation damage to lung are related to volume of lung irradiated, radiation dose rate, and quality of radiation, and also concomitant chemotherapy, previous radiotherapy, and steroid withdrawal have been considered to potentiate damaging effects of radiation. The augmentation of radiation damage on lung by cancer chemotherapeutic agents which are known to enhance radiation effect in lung. For the experiment, guinea pig were divided into 2 groups; irradiated group receiving a varying single dose of 10, 20 and 30Gy , and combined group which received a varying sinfle dose of irradiation and 150 mg/kg of cyclophosphamide injection 2 hours before irradiation. The result and summary of the experiment were as follows; 1. As compared with radiation reaction in lung induced by varying single doses, higher dose caused more severe degree of radiation reaction. 2. In radiographic examination, radiation pneumonitis began to appear 30 days after irradiation and showed progressive changes with volume decrease by atelectasis or fibrosis, with time interval. 3. The radiographic findings of radiation pneumonitis and fibrosis were more extensive at combined cyclophosphamide and irradiation group rather than irradiated group. 4. In light microscopic examination, there were progressive increase in alveolar collapse and macrophage infiltrates, proliferation of alveolar epithelial cells, and thickening of alveolar septae with fibrosis. 5. There were earlier onset and extensive degree of fibrosis in combined cycplphiosphamide and irradiation group as comparing irradiated group. 6. The degree of alveolar collapse and fibrosis in alveolar septae which occurred in 20Gy irradiation combined with cyclophosphamide was equal to that in 30Gy single dose irradiation and so dose-effect factor for cyclophosphamide was measured about 1.5. 7. The increased incidence and extent of radiation pneumonitis and fibrosis by combined cyclophosphamide could be considered as enhancement of radiation injury.