Differential enhancement of melphalan cytotoxicity in tumor and normal tissue by Fluosol-DA and oxygen breathing.
The addition of Fluosol-DA carbogen breathing to melphalan treatment of the FSa-IIC fibrosarcoma was assessed by tumor growth delay and cell survival assays. Melphalan (10 mg/kg) administered intraperitoneally (i.p.) was preceded by Fluosol-DA (0.3 ml) administered intravenously (i.v.) and followed by 1 hr of carbogen breathing; this resulted in a tumor growth delay of 9.5 +/- 1.4 days or an approximately 3-fold increase compared to melphalan alone. Melphalan produced about 1.7 logs of cell killing; neither carbogen breathing nor Fluosol-DA pretreatment altered the cell killing observed. There was a 10-fold increase in tumor-cell killing when Fluosol-DA was administered immediately prior to melphalan administration followed by carbogen breathing for 1 hr. Density gradient separation identified a population of denser FSa-IIC cells which showed increased sensitivity to melphalan after Fluosol-DA administration. There was no additional toxicity to bone marrow as measured by CFU-GM with the combination of melphalan/Fluosol-DA/O2 compared to melphalan alone.
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004338:Drug Combinations / Q000494:pharmacology; D004357:Drug Synergism; D005466:Fluorocarbons / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives; D008297:Male; D008558:Melphalan / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology*; D012119:Respiration
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D002245:Carbon Dioxide; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; C011700:carbogen; D008558:Melphalan; D010100:Oxygen