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Oleic Acid Incorporation Protects Cultured Hamster Fibroblasts from Oxygen-Induced Cytotoxicity^1,2,3,

Michael Kinter^*,,4, Douglas R. Spitz and Robert J. Robert^**

Department of ^* Microbiology Pathology ^** Pediatrics, University of Virginia Health Sciences Center, Charlottesville, VA 22908 Section of Cancer Biology, Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO 63108

The effects of oleic, linoleic and arachidonic acid on oxygen toxicity were evaluated in cultured hamster fibroblasts. Each fatty acid was incorporated separately using a protocol that resulted in dose-dependent increases in the respective cellular fatty acid content to as much as 20-fold greater than unsupplemented controls. Linoleic acid produced no changes in cell survival after 48 h treatment with 95% oxygen, regardless of fatty acid content of the cells. Oleic acid incorporation resulted in a dose-dependent increase in cell survival at 48 h in 95% oxygen, whereas arachidonic acid incorporation resulted in a dose-dependent decrease in cell survival at 48 h in 95% oxygen. No significant differences in amounts of linoleic or arachidonic acids were detected in control, oleic acid- enriched or linoleic acid-enriched cells during oxygen exposure. In cells enriched with arachidonic acid, exposure to oxygen significantly reduced the amounts of linoleic and arachidonic acid to 79 and 84%, respectively, of the amounts found in air-exposed cells. The results indicate that oleic acid incorporation into cells provides protection against 95% oxygen-induced cytotoxicity. In contrast, arachidonic acid incorporation led to sensitization of cells to 95% oxygen-induced cytotoxicity that was accompanied by a loss of polyunsaturated fatty acids. As a result, it would appear that in situations of increased oxidative stress, high monounsaturated fatty acid diets that increase cellular oleic acid content may provide a protective environment compared with high polyunsaturated fatty acid diets that increase cellular arachidonic acid content.

KEY WORDS: • hamster ovary fibroblasts • oleic acid • linoleic acid • arachidonic acid • oxidant injury

¹ Presented in part at the 63rd Annual Meeting of the Society for Pediatric Research, May 2–5, 1994, Seattle, WA [Kinter, M. T., Adams, D. T. & Roberts, R. J. (1994) Comparison of oxidative injury in oleic versus linoleic versus arachidonic acid fed cultured cells. Pediatr. Res. 35: 85A (abs.)].

² Supported by grants HL42057 and HL51469 from the National Institutes of Health.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 28 December 1995. Revision accepted 8 August 1996.