Potentiation of bleomycin toxicity by oxygen

The clinical usefulness of bleomycin is limited by pulmonary toxicity. Recent clinical observations indicate that the pulmonary toxicity is potentiated in patients who are exposed to elevated but nontoxic concentrations of O2. We studied the interactions of O2 and bleomycin using a murine model. Mice were divided into two groups. One group was continuously exposed to 40% O2 at 1 atmosphere while the other group breathed compressed room air. The elevated O2 concentration alone was not toxic to animals. Mice in each group received either 40 mg/kg of bleomycin or normal saline twice a week sc. Median survival of mice receiving bleomycin was shortened from 8.24 to 4.35 weeks when the animals were maintained on 40% O2 (P = 0.0001). We conclude that exposure to a nontoxic but elevated O2 concentration can potentiate the toxic effects of bleomycin.