The Pulmanary Toxicity after Treatment with Bleomycin in Combination with Hyperoxia

Chai, In; Lee, Hae Jin; Choi, Yong Woo; Sung, Choon Ho; Moon, Se Ho; Chung, Woon Hyok

Abstract

The bleomycin is a chemotherapeutic agent useful in the treatment of selected neoplasms, including non-seminomatous testicular carcinoma. An increased incidence of respiratory failure postoperatively in patients previously treated with bleomycin has been reported. And an increase in the toxicity of high concentration of oxygen in oxygen therapy has been demonstrated in rodents after administration of bleomycin. However, the use of an enriched inspired oxygen concentration 41% was reported not hazardous in a testicular cancer population who were exposed to significant doses of bleomycin. The pulmonary toxicity of bleomycin therapy in combination with high oxygen exposure is still controversial. The aim of this study is to analyze the effect of exposure to 50% oxygen in the mice pretreated with bleomycin. Bleomycin were administered intraperitoneally to the mice, 4 mg/ kg twice a week for 5 weeks. After administeration of bleomycin to the mice, the half of the miee, the experimental group, were exposed to 50% oxygen for 24 hours. And the other control group were exposed to room air. Morphometric analysis with light microscopy was performed to the following parameters; number of total pulmonary cell count, percentage of consolidation of lung parenchyma and degree of intensity of fibrosis of lung parenchyma. The area of diseased lung was increased in mice given with bleomycin and hyperoxia compared with that of those treated with bleomycin only. The results were as follows, l) In the control group given 4 mg/kg bleomycin and room air, the number of total pulmo- nary cell count were 36.21+/-6.53/10(-8) m(2) and the percentage of consolidation was 1.2+/-0.4%. 2) In the experimental group given with 4 mg/kg bleomycin and 50% oxygen for 24 hrs, the number of total pulmonary cell count were 59.67+/-9.13/10(-8) m(2) and the percentage of area of consolidation of lung parenchyma was 5.8+/-2.3%, 3) Fibrosis of the lung parenchyma was seen only in the experimental group to which oxygen was given after administration of bleomycin. In conclusion, this study demonstrated that hyperoxia potentiated the pulmonary damage by bleomycin in the mice.