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

Departments of Medicine [M. M. G., J. A. R., C. P. B.] and Biochemistry [I. S.], University of Iowa College of Medicine, Iowa City, Iowa 52242

We investigated the effect of fatty acid alteration on the thermosensitivity of a mammalian tumor cell, the L1210 lymphoblastic leukemia. Cells growing in Roswell Park Memorial Institute Medium 1640 with 5% fetal calf serum were modified with respect to their fatty acid composition by supplementing the media with either 40 µM docosahexaenoic acid (22:6) or oleic acid (18:1). A soft-agar clonogenic assay was used to assess viability following hyperthermic exposure. Cells grown in 22:6-supplemented media were more sensitive (D₀ 18.7 ± 0.4 min), and cells grown in 18:1-supplemented media were less sensitive (D₀ 46.2 ± 1.6 min) to a 42° exposure than were cells grown in unsupplemented media (D₀ 27.5 ± 1.5 min) (p < 0.001 for all comparisons). These contrasting effects on thermosensitivity increased as the concentration of supplemental fatty acid increased from 0 to 40 µM and were apparent at all temperatures from 41 to 44°. When compared to cells grown in unsupplemented media, those grown in 22:6-supplemented media contained 300% more polyenoic and 70% less monoenoic fatty acid in their cell phospholipids, while those grown in 18:1-supplemented media contained 37% less polyenoic and 17% more monoenoic fatty acid. Similar changes were noted in neutral lipid fatty acid composition, while no changes were noted in cellular cholesterol or phospholipid content. Electron spin resonance studies suggested a significant increase in membrane fluidity when cells were grown in 22:6-supplemented media and a decrease when cells were grown in 18:1-supplemented media. These data demonstrate that modification of the cellular fatty acid composition of a mammalian tumor cell dramatically affects its thermosensitivity.

¹ This investigation was supported by Grant CA 17283 awarded by the National Cancer Institute, Department of Health and Human Services.

² Supported by NIH Training Grant T32 HL 07344. To whom requests for reprints should be addressed, at the Department of Medicine, University Hospitals, Iowa City, Iowa 52242.

³ Recipient of USPHS Career Development Award CA 00324.

Received 1/25/82. Accepted 6/15/82.