GAMMA-LINOLENIC ACID (GLA) IS CYTOTOXIC TO 36B10 MALIGNANT RAT ASTROCYTOMA-CELLS BUT NOT TO NORMAL RAT ASTROCYTES

This study compares the effect of gamma-linolenic acid (GLA) and its p recursor linoleic acid (LA) on survival of 36B10 malignant rat astrocy toma cells and 'normal' rat astrocytes. GLA was cytotoxic to 36B10 cel ls but not to astrocytes; By contrast, LA supplementation did not affe ct the survival of either cell types. There were minor differences in the uptake, distribution and use of radiolabelled GLA and LA by the 36 B10 cells and astrocytes. GLA and LA supplementation increased the tot al polyunsaturated fatty acid (PUFA) content of the cells indicating i ncreased oxidative potential. However, elevated levels of 8-isoprostan e, an indicator of increased oxidative stress, were only observed in t he GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA-enriched 36B10 cells blocked the cytotoxic effect. Further, GLA e nhanced the radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox blocked the GLA-mediated increase in astrocytoma c ell radiosensitivity. LA did not affect the radiation response of eith er cell type. While cyclo-oxygenase inhibitors did not affect GLA cyto toxicity, they blocked the enhanced radiation response of GLA-suppleme nted cells. The lipoxygenase inhibitor NDGA did not affect the toxicit y produced by GLA. Thus, GLA is toxic to the neoplastic astrocytoma ce lls but not to normal astrocytes.