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Effect of Cellular Fatty Acid Alteration on Adriamycin Sensitivity in Cultured L1210 Murine Leukemia Cells¹

Department of Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242

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 µM 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 µM, 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 < 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 µM. 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.

¹ This investigation was supported by Grant CA31526 awarded by the National Cancer Institute, Department of Health and Human Services.

² Recipient of USPHS Career Development Award CA00324. To whom requests for reprints should be addressed, at the Department of Medicine, University Hospitals, Iowa City, IA 52242.

Received 10/ 7/83. Accepted 2/ 9/84.