Effect of Fluosol-DA/O2 on the antitumor activity and pulmonary toxicity of bleomycin.
The effect of an oxygen-carrying perfluorochemical emulsion on bleomycin antitumor activity and pulmonary toxicity was examined. Fluosol-DA (0.3 ml/mouse, i.v.), combined with bleomycin (10 or 15 mg/kg, i.p.) and a 2 h exposure to 95% oxygen (BFO) increased by five- to six-fold the tumor growth delay of FSaIIC fibrosarcoma compared to bleomycin alone (B). Only a slight increase in tumor growth delay was noted with the incomplete combinations of bleomycin and O2 (BO) and bleomycin and Fluosol-DA (BF). When bleomycin (10 mg/kg) was co-administered with 0.3 ml Fluosol-DA and 95% O2, cell survival was reduced ten-fold compared to that seen with bleomycin alone. In contrast, the surviving fraction of cells obtained from FSaIIC tumors treated in vivo indicated that 0.3 ml Fluosol-DA per mouse or a 2 h exposure to 95% O2 did not markedly alter the effects of bleomycin alone. The pulmonary effects of the BFO combination were assessed during the course of the therapy by bronchoalveolar lavage (BAL) analysis and pulmonary hydroxyproline (OH-Pro) content. Mice treated with this combination had a 20-fold increase in total numbers of cells obtained in the BAL compared to control animals. An increased cellularity in the lungs was also seen morphologically. The composition of the cells in the lavage fluid was altered after BFO but not BO treatment and reflected a neutrophilic influx. Furthermore, total protein recovered in the BAL fluid was increased 5-fold in the BFO treatment group compared to that in the control mice. Pulmonary OH-Pro, an index of collagen and fibrosis, was unaffected acutely after three treatments of either BFO or BO compared to control mice. Thus, Fluosol-DA and O2 can enhance the antitumor activity of bleomycin. The increased pulmonary cellularity suggests that this combination may also have adverse effects on lung tissue.
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002478:Cells, Cultured; D004338:Drug Combinations / Q000008:administration & dosage / Q000009:adverse effects; D004357:Drug Synergism; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000009:adverse effects; D006895:Hydroxyethyl Starch Derivatives; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000008:administration & dosage* / Q000009:adverse effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000473:pathology
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D001761:Bleomycin; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D010100:Oxygen