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Differential enhancement of melphalan cytotoxicity in tumor and normal tissue by fluosol-DA® and oxygen breathing

✍ Scribed by Beverly A. Teicher; Sylvia A. Holden; Christopher M. Rose


Publisher
John Wiley and Sons
Year
1985
Tongue
French
Weight
515 KB
Volume
36
Category
Article
ISSN
0020-7136

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✦ Synopsis


The addition of Fluosol-DAB 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 (Lv.) and followed by I hr of carbogen breathing; this resulted in a tumor growth delay of 9.5 f 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/Oz compared to melphalan alone.


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