Non-lethal hyperoxic potentiation of lung disease in the rat following subcutaneous administration of bleomycin.

Rats were treated with subcutaneous injections of either saline or 1, 3, or 5 units of bleomycin (BLM) each day for 5 days (5, 15, or 25 units total dose). One half of each group of animals was exposed to 80% oxygen for 4 days during BLM dosings. Rats treated with both 25 units BLM and hyperoxia died after being returned to room air. All remaining rats were sacrificed 6 weeks following the end of treatment. Of the BLM rats in room air, only the lungs of the 15-unit group exhibited histological change, a mild diffuse interstitial disease. Both lower dose groups demonstrated slight increases in hydroxy-proline (OHP) content, a marker of collagen deposition or lung injury. The lungs of BLM rats exposed to hyperoxia demonstrated greater increases in total lung OHP levels. The lungs of the 15-unit group demonstrated lesions consistent with diffuse interstitial pulmonary fibrosis. Short-term, sublethal hyperoxia clearly potentiated injury in the rat following subcutaneous BLM treatment as assessed by either lethality or markers of pulmonary pathology.