Effect of Fluosol-DA/O2 on tumor-cell and bone-marrow cytotoxicity of nitrosoureas in mice bearing FSA-II fibrosarcoma.
The perfluorochemical emulsion, Fluosol-DA, combined with carbogen breathing, potentiates the effects of radiation and a number of chemotherapeutic agents in several rodent tumors. The interaction of Fluosol-DA with drugs may be quite complex. In addition to increasing the oxygen supply in the tumor, Fluosol-DA may alter the pharmacokinetics of the drug and function as a drug delivery system. A series of 4 nitrosoureas of varying lipophilicity were administered as single doses intravenously (i.v.) to C3H/Be/FeJ mice bearing subcutaneous FSa-IIC fibrosarcomas. Doses of 40 mg/kg of CCNU, 15 mg/kg of BCNU, 20 mg/kg of MeCCNU and 15 mg/kg of chlorozoticin followed by 2 hr of breathing 95% oxygen produced tumor growth delays of 7.5, 4.0, 3.8 and 2.7 days, respectively. When the drug injection was followed immediately by 0.3 ml of Fluosol-DA and 2 hr of breathing 95% oxygen, the tumor growth delay produced by CCNU, BCNU, MeCCNU and chlorozoticin increased 2-fold, 10-fold, 4.5-fold and 3.5-fold, respectively. Administration of the drugs in Fluosol-DA followed by 2 hr of 95% oxygen breathing resulted in a 3.5-fold increase in tumor growth delay with CCNU, a 17-fold increase with BCNU, a 12.5-fold increase with MeCCNU and a 6-fold increase with chlorozoticin compared to drug and 95% oxygen breathing. These results are quantified in terms of cell survival by the tumor excision assay. Effects on the bone marrow from each treatment were measured using the granulocyte-monocyte colony-forming units (CFU-GM) assay. There was no correlation between the lipophilicity of the nitrosoureas tested and the tumor growth delay produced by each treatment.