Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very 
little is known of the mechanisms underlying the development of lung injury, 
especially after intravenous administration, or how it can be modulated. In this 
study acute lung injury induced by bleomycin has been examined in rats by 
assessment of alveolar lavage cell profiles, histological examination, and 
measurement of the total pulmonary extravascular albumin space. Intratracheal 
instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of 
inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of 
the alveolar walls, and up to an eight fold increase in the total pulmonary 
extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 
mg produced no detectable injury when assessed in these ways. Exposure to 
hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury 
similar to that produced by intratracheal bleomycin. A much more severe injury 
followed administration of intravenous bleomycin after an exposure to hyperoxia, 
which itself resulted in lung injury; but lung injury was still detectable after 
bleomycin when the exposure to hyperoxia was insufficient to induce changes in 
control animals. Lung injury was not observed when the exposure to hyperoxia 
preceded bleomycin treatment. These results indicate the importance of oxygen in 
the pathways leading to acute lung injury following intravenous bleomycin. We 
conclude that exposure to oxygen might induce lung injury during and after 
bleomycin treatment, and suggest that in these circumstances oxygen therapy 
should be kept to a minimum.