Exacerbation of tallysomycin toxicity in rats by concurrent exposure to sublethal hyperoxia

Rats were given daily subcutaneous injections of tallysomycin S10b (TLM) or bleomycin (BLM) for 6 days (1.25 or 2.50 mg/day). One half of each group was exposed to 80% oxygen for the last 4 days of drug treatment and then returned to room air. TLM produced marked mortality in contrast to equal doses of BLM. Exposure to 80% oxygen increased the lethality of either TLM and BLM treatments. The cause of death appeared to be related to pulmonary changes. Two weeks following the end of treatment in the low dose experiment, the lungs of surviving BLM-hyperoxia, TLM, and TLM-hyperoxia rats demonstrated severe vascular damage consistent with both endothelial cell and smooth muscle proliferation in pulmonary blood vessels. BLM-hyperoxia rats also demonstrated a more typical diffuse interstitial disease. All treatments produced an increase in lung-to-body weight ratio and a decrease in vital capacity and total lung compliance, as compared to age-matched controls. TLM toxicity was exacerbated by short-term exposure to 80% oxygen. Morbidity and mortality appeared to be related to severe lung changes similar to the hyperoxic potentiation of BLM lung disease.