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Summary Decreased membrane rigidity is one of the characteristics of malignant cells, resulting in part from the desaturation of stearic acid into oleic acid. In this study we investigated the influence of stearic acid on tumour cell inhibition in vitro and tumour development in vivo. Stearic acid inhibited the colony-forming ability of 4 out of 5 rat and two human tumour continuous cell lines in vitro. In contrast, the colony-forming ability of rat fibroblasts was not inhibited and that of human foetal lung fibroblasts was inhibited at a higher dose than that required to inhibit human tumour cell lines. Using a model of rat mammary carcinoma induced by nitroso-methyl urea (NMU) the subcutaneous injection of stearic acid at weekly intervals prevented tumour development in 5 to 10 rats. Using iodostearic acid twice weekly, 11 of 19 rats were alive and tumour free at week 22 whilst all of 14 animals injected with NMU alone had died of tumour by the 16th week. The ratio of stearic to oleic acids in erythrocyte membranes was significantly reduced in the tumourbearing rats, but was normal in tumour-free animals treated with stearic or iodostearic acid. These preliminary data indicate that stearic acid inhibits tumour development in rats.The regulation of membrane rigidity is essential for homeostasis (Cooper, 1977) and the metabolic rates of many essential cell enzymes depend on it (Sandemann, 1979). In general, decreased membrane rigidity leads to increased cell metabolism and also higher division rates, features characteristic of the malignant cell. Corvin et al. (1977) have also shown that alteration of membrane lipid structure may change the cancer cell phenotype. The evidence for decreased membrane rigidity in malignant cells is derived from direct physical measurements and lipid analysis. Using fluorescent probes and magnetic resonance studies, decreased microviscosity (decreased membrane rigidity) was found in plasma membranes, as well as in isolated lipid vesicles from leukaemic cells (Petitou et al., 1978;Mountford et al., 1986). Fatty acid analysis of lipids extracted from transformed cells, cell lines, leukaemic cells and solid tumour tissue showed a consistent increase in the oleic acid content relative to stearic acid Wood et al., 1985).The normal metabolic flow results in conversion of the saturated stearic acid to the monounsaturated oleic acid by the enzyme complex delta 9 desaturase. The ratio of stearic to oleic acid, the so-called saturation index (SI), reflects the activity of this enzyme . A significant decrease in the SI of red blood cell membranes was noted in a range of human and animal malignancies (Habib et al., 1987b), and it was suggested that this index could be used as a tumour marker. It has also been reported that there is a decrease in the SI of red blood cell membranes in patients suffering from the Acquired Immune Deficiency Syndrome .We have noted previously that interferon inhibits the desaturation of stearic acid in vitro (Apostolov & Barker, 1981) and that interferon treatment...

Segemental and focal pathological changes were found in the glomeruli and tubules of postoperative renal-biopsy specimens from seven cases of clinically confirmed endemic (Balkan) nephropathy. In the glomeruli, there was mesangial reaction and segmental thickening of the basement membrane with subendothelial and membranous depositions. In the tubules there was spongiform degeneration and fusion of cells. In all the cells of the nephron numerous cytoplasmic vesicles containing free and budding particles (80-200 nm) were found. These particles had the characteristics of a coronarivus. Balkan nephropathy occurs almost exclusively in people who have been in close contact with pigs. Coronaviruses have been isolated from pigs, and it is suggested that a slow coronavirus infection causes endemic nephropathy in man.

Total lipid extracts of erythrocyte cell membranes from 60 patients with documented malignancies, 41 patients with various acute and chronic diseases, and 40 healthy subjects were analysed. The results were expressed as ratios of stearic to oleic acid, reflecting the diegree of desaturation of stearic acid. The mean ratios for the healthy subjects and controls without cancer were 1-5 (SD 0 27) and 1 45 (0 28), respectively, whereas the ratios for patients with malignancies were consistently lower than the cut off point of 1-0, with a mean of 0 69 (0-15) (p <0 001). The desaturation ratio was also significantly lower (p <0 001) in the group with recurrent tumours (mean 0 75 (0 04)) compared with those with no evidence of recurrent tumours (mean 1-55 (0 27)).It is suggested that the increased unsaturation (oleic acid) in the circulating erythrocytes may be useful in the diagnosis and postoperative monitoring of patients with cancer.

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