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Differential enhancement of melphalan cytotoxicity in tumor and normal tissue by fluosol‐DA ® and oxygen breathing
Author(s) -
Teicher Beverly A.,
Holden Sylvia A.,
Rose Christopher M.
Publication year - 1985
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910360512
Subject(s) - melphalan , carbogen , medicine , fibrosarcoma , nitrogen mustard , toxicity , chemotherapy , pharmacology , anesthesia , pathology , cyclophosphamide , oxygenation
Abstract 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 FSaIIC 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/O 2 compared to melphalan alone.