Teteraene and pentaene leukotrienes: Selective production from murine mastocytomo cells after dietary manipulation

Abstract

A neoplastic mast cell tumor was grown in mice which had been raised since birth on a diet enriched with eicosapentaenoic acid. Intact harvest mastocytoma cells were stimulated with calcium ionophpore A23187 to produce lipoxygenase products from the polyunsaturated fatty acids liberated from the cellular membranes. Leukotriene B4, B5, C4 and C5 were isolated and characterized by HPLC retention time, ultraviolet absorption spectrometry and mass spectrometry. The arachidonic acid content of the mast cell tumor lipids was altered from 9.2 to 3.9 mole% while eicosapentaenoic acid increased from 0.5 to 4.5 mole % in response to the fish oil-supplement diet.The relative amount of arachidonic and eicosapentaenoic acids (3.9 and 4.5 mole % respectively) were associated with similar amounts of LTB4 and LTP5 synthesized by the cells. These results suggest that the epoxide leukotrine (LTA) derivative can be made efficiently from either arachidonic or eicosapentaenoic acids when both are present in cellular lipids. In contrast, the ratio of LTC4 to LTC5 (10 to 1) indicates that the reaction of LTA with glutathione may be critically dependent upon the structure of the unsaturated fatty acid with the ratio of LTC4/LTB4 (2.0) more than 10 times greater than that (0.16) for LTC5/LTP5.