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  • Title: Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells.
    Author: Guffy MM, North JA, Burns CP.
    Journal: Cancer Res; 1984 May; 44(5):1863-6. PubMed ID: 6231987.
    Abstract:
    We have investigated the effect of cellular fatty acid alteration on Adriamycin cytotoxicity using the L1210 lymphoblastic leukemia cell line. Cells growing in Roswell Park Memorial Institute Medium 1640 with 5% fetal bovine serum were modified with respect to fatty acid composition by supplementing their growth medium with 32 microM docosahexaenoic acid (22:6) or oleic acid (18:1). A soft agar clonogenic assay was then used to assess survival following incubation with Adriamycin. When exposed to the drug at a concentration of 0.4 microM, cells grown in the 22:6-supplemented medium were more sensitive (min of drug treatment required to reduce survival by 63% on the exponential portion of the survival curve, 64.9 +/- 4.2 min) to the cytotoxic effects of Adriamycin than cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 106 +/- 9.7 min) (p less than 0.005). Cytotoxicity of L1210 cells grown in 18:1-supplemented medium was similar to that of cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 126.6 +/- 9.1 min). The heightened sensitivity to Adriamycin of cells whose medium contained 22:6 increased as the concentration of fatty acid used to supplement the growth medium was increased. The cytotoxicity was also a function of the concentration of Adriamycin from 0.1 to 1.6 microM. When compared to cells grown in unsupplemented medium, those grown in 22:6-supplemented medium contained 3- to 4-fold more polyunsaturated fatty acids in their phospholipids, with a resultant doubling in the mean number of double bonds per fatty acid molecule. These data demonstrate that modification of cellular fatty acid composition may dramatically affect the sensitivity of a tumor cell to Adriamycin.
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