Surface-specific electrical occlusal caries diagnosis: reproducibility, correlation with histological lesion depth, and tooth type dependence

We investigated the lipid metabolism in primary cultured hepatocytes to elucidate the causes of hyperlipidemia, increased cholesteryl esters, and decreased triglyceride levels in the livers of daunomycin-nephrotic rats. The incorporation of 14C-palmitate into phospholipids and triglycerides in primary cultured hepatocytes and medium was similar in daunomycin-nephrotic and control rats. The incorporation of 14C-acetate into phospholipids, triglycerides, cholesterol, cholesteryl esters, and total fatty acids in primary cultured hepatocytes was increased in daunomycin-nephrotic rats. The radioactivity of phospholipids, triglycerides, cholesterol, cholesteryl esters, and very-low-density lipoprotein lipids in medium was increased in the hepatocytes of daunomycin-nephrotic rats using 14C-acetate as a precursor. The increased cholesterogenesis and the increased secretion of triglycerides synthesized from acetate by hepatocytes may be due to an increased cholesteryl ester content and a decreased triglyceride content in the livers of daunomycin-nephrotic rats. The increased secretion of lipids synthesized from acetate by hepatocytes may be due to increased accumulation of lipids in serum and very-low-density lipoprotein in daunomycin-nephrotic rats.     

Kinetic characteristics and regulation of HDL cholesteryl ester and apolipoprotein transport in the apoA-I-/- mouse

The concentration dependence and tissue distribution of high density lipoprotein (HDL) cholesteryl ester and apolipoprotein (apo) transport were determined in apoA-I knockout mice (apoA-I-/-) that lack normal HDL in plasma. Rates of HDL cholesteryl ester clearance were highly sensitive to plasma HDL cholesteryl ester concentrations with clearance rates falling by 80% in the liver and by 95% in the adrenal glands when plasma HDL cholesteryl ester concentrations were acutely raised to levels normally seen in control mice (approximately 50 mg/dl). With the exception of the brain, saturable HDL cholesteryl ester uptake was demonstrated in all tissues of the body, with the adrenal glands and liver manifesting the highest maximal transport rates (Jm). The plasma concentration of HDL cholesteryl ester necessary to achieve half-maximal transport (Km) equaled 4 mg/dl in the adrenal glands and liver; as a consequence, HDL cholesteryl ester uptake by these organs is maximal (saturated) at normal plasma HDL concentrations in the mouse. When expressed per whole organ, the liver was the most important site of HDL cholesteryl ester clearance accounting for approximately 72% of total HDL cholesteryl ester turnover at normal plasma HDL concentrations. HDL cholesteryl ester transporter activity and scavenger receptor type B1 (SR-BI) protein and mRNA levels were not up-regulated in any organ of apoA-I-/- mice even though these animals lack normal HDL.     

In vitro effect of garlic powder extract on lipid content in normal and atherosclerotic human aortic cells

In the present study, the mechanism of the in vitro effect of garlic powder extract (GPE) on lipid content of cultured human aortic cells was investigated. The addition of GPE abolished atherogenic blood serum-induced accumulation of free cholesterol, triglycerides, and cholesteryl esters in smooth muscle cells derived from uninvolved (normal) intima. In cells isolated from atherosclerotic plaque, GPE lowered these lipids. GPE inhibited lipid synthesis both in normal and atherosclerotic cells. It inhibited acyl-CoA:cholesterol acyltransferase activity that participates in the cholesteryl ester formation and stimulated cholesteryl ester hydrolase that degrades cholesteryl esters. This may explain the lipid reduction caused by GPE in atherosclerotic cells. GPE inhibited the uptake of modified low density lipoprotein and degradation of lipoprotein-derived cholesteryl esters, thus considerably reducing the intracellular accumulation of cholesteryl esters. This suggests the mechanism responsible for the prevention of lipid accumulation in aortic cells caused by atherogenic blood serum.     

Effects of ID-540 on averaged photopalpebral reflex in man

Twelve hyperlipidemic patients on long term treatment with a lipid lowering diet enriched in polyunsaturated fatty acids and with clofibrate were supplemented with vitamin E (400 mg/day). The effect on serum lipoprotein concentration, plasma lipid fatty acid composition, and adipose tissue lipoprotein lipase activity was studied. No additional lipid-lowering effect was registered during a treatment period of 4 months. A slight increase in total serum cholesterol concentration and in high density lipoprotein concentration was probably attributable to seasonal variations in serum lipoprotein concentrations. No major changes of fatty acid composition in plasma cholesteryl esters or triglycerides were recorded. However, an increased relative amount of arachidonic acid and a reduced amount of palmitic acid in the plasma phospholipids after 2 months was possibly caused by the vitamin E therapy.     

Effect of temperature and viscosity on the motility of the spirochete Treponema denticola

Two adult siblings with early onset dementia are described. At presentation, in their early 30s, they showed poor judgment and disinhibition. A progressive dementia ensued over several years. Brain MRI disclosed diffusely increased T2 signal in the cerebral white matter, suggestive of a leukodystrophy. Numerous lysosomal enzyme assays including leucocyte arylsulphatase A and galactocerebrosidase activities, plasma and fibroblast very long chain fatty acid concentrations, and urinary sulphatide concentrations were normal, as were CSF analyses. A brain biopsy disclosed periodic acid Schiff (PAS) and Sudan black positive material in perivascular macrophages which, by electron microscopy, consisted of stacks of straight or curvilinear paired membranes within angulate lysosomes, indicative of abnormal glycolipid accumulation. The combination of clinical, radiological, biochemical, and pathological features of this degenerative disease is not consistent with that of any of the known leukodystrophies or lysosomal storage disorders. These findings suggest a previously undescribed familial glycolipid storage disorder causing an adult onset leukodystrophy and presenting with behavioural symptoms that mimic a psychiatric disorder.     

A histochemical study of iron-positive cells in the developing rat brain

The establishment of normal iron levels in the neonatal brain is critical for normal neurological development. Studies have shown that both iron uptake and iron concentration in the brain are relatively high during neonatal development. This histochemical study was undertaken to determine the pattern of iron development at the cellular level in the rat forebrain. Iron-stained cells were observed as early as postnatal day (PND) 3, which was the earliest time point examined. At PND 3, there were four major foci of iron-containing cells: the subventricular zone and three areas within the subcortical white matter. These latter foci are associated with myelinogenic regions. The blood vessels were prominently stained for iron throughout the brain. At PND 7, as in PND 3, the majority of the iron-containing cells were in white matter. However, there were also patches of iron staining located specifically in the layer IV of the somatosensory cortex. These cortical patches were no longer visible by PND 14. At PND 14, numerous iron-stained cells were dispersed throughout white matter regions and the tanycytes aligning the third ventricle were prominently stained. The blood vessel staining was less prominent than at earlier time periods. By PND 28, the adult pattern of iron staining was emerging. Iron-stained cells were aligned in rows in white matter and had an apparent preference for a location near blood vessels. This clustering of iron-positive cells around blood vessels gave the white matter a "patchy" appearance. The pattern of development, cell distribution, and morphological appearance of the iron-stained cells are consistent with that reported for oligodendrocytes. That iron-positive cells in the neonate may be oligodendrocytes is consistent with the reports for iron staining in adult brains. The recent reports that oligodendrocytes are highly susceptible to oxidative damage would be consistent with the high iron levels found in these cells. These results indicate that oligodendrocytes play a major role in the development of iron homeostasis in the brain. The role of iron in oligodendrocytes may be associated with metabolic demands of myelinogenesis, including cholesterol and fatty acid synthesis. However, these cells may be a morphologically similar but functionally distinct subset of oligodendrocytes whose function is to regulate the availability of iron in the brain.     

Cholesteryl ester accumulation in macrophages treated with oxidized low density lipoprotein

The ability of CuSO4- and hypochlorite-oxidized LDL to promote cholesterol accumulation in macrophages was examined. Both CuSO4- and hypochlorite-oxidized LDL were rapidly metabolized by mouse peritoneal macrophages to a level approximately 10 times that observed for native LDL and both modified lipoproteins increased the accumulation of unesterified cholesterol. However when each modified lipoprotein was incubated with macrophages for 40h, only hypochlorite-oxidized LDL produced significant accumulation of cholesteryl esters, with levels approaching 85 micrograms/mg cell protein. This finding was verified by nile red staining. The cholesteryl ester content of cupric sulfate-modified LDL was found to be significantly decreased when compared to either native or hypochlorite-modified LDL promotes massive cholesteryl ester accumulation because the cholesteryl ester content of the LDL particle is preserved.     

Changes in the cholesterol and phospholipid content of mouse spleen after Raucscher leukemia virus infection

The effect of Rauscher Leukemia Virus (MuLV-R) infection on the lipid composition of mouse spleen from BALB/c mice was investigated. Drastic changes in the lipid composition of the spleen as a result of tumor growth induced by the virus could be demonstrated at 21 days after infection. The molar ratio of cholesterol to phospholipids was found to be low, while a shift within the choline containing phospholipid classes resulted into a lower sphingomyelin and a higher phosphatidyl choline content of the MuLV-R infected spleen. The cholesterol ester content increased more than two-fold during tumor growth, and shifts in the fatty acid patterns of the lipids were demonstrated.     

Sterol and steryl ester regulation of phospholipase A2 from the mosquito parasite Lagenidium giganteum

Lagenidium giganteum, a facultative parasite of mosquito larvae, cannot synthesize sterols, and requires an exogenous source of these lipids in order to enter its reproductive cycle. This parasite grows vegetatively in the absence of sterols, but requires cholesterol or structurally related compounds to produce motile zoospores, which are the only stage capable of infecting mosquitoes. Sterols structurally related to cholesterol and some steryl esters inhibited the activity of L. giganteum phospholipase A2 (PLA2), an enzyme that hydrolyzes fatty acids from the sn-2 position of glycerophospholipids. Sterols that induce reproduction inhibited L. giganteum PLA2 activity, while sterols and steroids that do not support sporulation had minimal effect. Most steryl esters had no effect on enzyme activity, but cholesteryl arachidonate (CA) was a potent inhibitor of parasite PLA2. Not all enzymes partly purified using a DEAE-Sephacel column were affected by these lipids, demonstrating selective inhibition of specific enzymes. Potency was enhanced by up to several orders of magnitude if epoxy fatty acids were esterified to the cholesterol nucleus. The steryl ester pool was dynamic during morphogenesis, and the fatty acid composition of the steryl esters did not mimic total cell or membrane (glycerophospholipid) fatty acid composition as L. giganteum proceeded through its growth cycle. Synthesis of CA and monoepoxy CA by the parasite was confirmed using electrospray mass spectrometry and collision-induced dissociation. Steryl derivatives selectively inhibited PLA2 enzymes from bovine pancreas, snake venom, and human cytoplasmic 85-kDa PLA2.     

Decreased resistance against in vitro oxidation of LDL from patients with familial defective apolipoprotein B-100

Familial defective apolipoprotein B-100 (FDB) is caused by a mutation in the receptor-binding region of apolipoprotein B-100, the structural protein of the low-density lipoprotein (LDL) particle. We studied the effect of this mutation on the composition and susceptibility to oxidative modification of LDL in patients with FDB. Twenty Dutch carriers of the mutation identified in a family study were matched with 20 unaffected siblings of similar age and sex. The mean concentration of LDL cholesterol was 5.19 +/- 0.94 versus 2.9 +/- 0.5 mmol/L in control subjects (P < .0001). Measurement of LDL oxidizability in vitro by continuously monitoring conjugated-diene absorbance showed that LDL from FDB patients was significantly less resistant against oxidation (lag time, 90 +/- 22 minutes versus 108 +/- 21 minutes; P < .05); furthermore, the maximal rate of diene production and total diene production were also significantly increased. Analysis of the chemical composition revealed an increased relative content of cholesteryl esters and reduced content of protein in the LDL of FDB patients (cholesterol-to-protein ratio, 1.54 +/- 0.24 versus 1.25 +/- 0.23; P < .01). The relative amount of arachidonic acid in LDL was increased and that of stearic acid was decreased. The vitamin E (alpha-tocopherol) content per gram of LDL protein was similar to that in control subjects. The relative amount of cholesteryl esters and protein in LDL as well as the fatty acid composition were significantly correlated with LDL oxidizability. Thus, compositional factors in LDL resulting in increased susceptibility to oxidative modification may contribute to the increased risk of premature vascular disease in FDB.     

Diet modification alters plasma HDL cholesterol concentrations but not the transport of HDL cholesteryl esters to the liver in the hamster

These studies were undertaken to investigate the mechanism whereby diet modification alters the plasma concentration of high density lipoprotein (HDL) cholesteryl ester and apoA-I and to determine whether diet-induced alterations in circulating HDL levels are associated with changes in the rate of reverse cholesterol transport. Rates of HDL cholesteryl ester and apoA-I transport were measured in hamsters fed a control low-cholesterol, low-fat diet or the same diet supplemented with soluble fiber (psyllium) or with cholesterol and triglyceride (Western-type diet). The Western-type diet increased the plasma concentration of HDL cholesteryl ester by 46% compared to the control diet and by 86% compared to the psyllium-supplemented diet; nevertheless, the absolute rates of HDL cholesteryl ester transport to the liver were identical in the three groups. Diet-induced alterations in circulating HDL cholesteryl ester levels were due to changes in the rate of HDL cholesteryl ester entry into HDL (whole body HDL cholesteryl ester transport) and not to regulation of HDL cholesteryl ester clearance mechanisms. The Western-type diet increased the plasma concentration of HDL apoA-I by 25% compared to the control diet and by 45% relative to the psyllium-supplemented diet. Diet-induced alterations in plasma HDL apoA-I concentrations were also due entirely to changes in the rate of apoA-I entry into HDL (whole body HDL apoA-I transport). These studies demonstrate that the absolute flux of HDL cholesteryl ester to the liver, which reflects the rate of reverse cholesterol transport, remains constant under conditions in which plasma HDL cholesteryl ester concentrations are altered over a nearly 2-fold range by diet modification.     

Increased cholesterol content and esterification in rabbit aortic medial cells cultured in hyperlipidemic serum

Cells of early atherosclerotic lesions have an increased content of cholesteryl esters and enhanced rate of cholesterol esterification. The present study was carried out to elucidate whether these changes could be reproduced in a purely in vitro system. Cultures of rabbit aortic medial cells were incubated in a medium containing 10% of either normal rabbit serum (control cells) or serum from rabbits with cholesterol-induced hyperlipidemia (hyperlipidemic cells). The incorporation rate of [1-14C]oleate into cellular cholesteryl esters increased two- to threefold after four hours' incubation with hyperlipidemic serum and remained elevated during the rest of the eight days' study. After seven days' incubation the hyperlipidemic cells incorporated significantly more (+13%) oleate into triglycerides and significantly less (-15%) oleate into phospholipids than did the control cells. Cholesteryl ester content of the hyperlipidemic cells rose steeply for about two days, with a slower rise thereafter. In hyperlipidemic cells the esterified cholesterol content was significantly higher (315 ng/mug DNA) than in the control cells (79 ng/mug DNA). Hyperlipidemic cells showed a slow but significant rise of free cholesterol as well (from 1.15 mug/mug DNA in control to 1.50 mug/mug DNA). The results indicate that lipid changes resembling those in early atherosclerotic lesions can be brought about in vitro 0y treatment of aortic cells with hyperlipidemic serum.     

Glutathione modulates lipid composition of human colon derived HT-29 cells

Glutathione (GSH) is important in maintaining intracellular thiol status. The present study looked at the effect of GSH depletion on lipid composition of colon-derived HT-29 cells. GSH was depleted in HT-29 cells by incubation either with buthionine-S, R-sulfoximine (BSO) or diethylmaleate (DEM). GSH was restored during early periods of cells growth by supplementation of growth medium with either GSH ester or N-acetyl cysteine (NAC). Lipids were analysed following GSH depletion and supplementation. Among the neutral lipids, an increase in free cholesterol and diacylglycerol and decrease in cholesteryl ester and triacylglycerol were seen in GSH-depleted cells as compared to control cells. There were no detectable free fatty acids either in control or GSH-depleted cells. Among the phospholipids, a decrease in phosphatidylcholine and phosphatidylinositol and an increase in phosphatidylethanolamine were observed. These changes were a completely reversed by supplementation of BSO-treated cells with GSH ester and partially reversed by N-acetyl cysteine. These results suggest that the GSH status of the cell plays an important role in the lipid composition of the cells.     

Hydrolysis of phosphatidylcholine by hepatic lipase in discoidal and spheroidal recombinant high-density lipoprotein

Hepatic lipase (HL) hydrolysis of phosphatidylcholine (PC) was studied in recombinant high-density lipoprotein particles (r-HDL). r-HDL were made from cholate mixed micelles that contained PC, apo AI, and, in some cases, unesterified cholesterol. r-HDL were characterized using chemical composition, nondenaturing gradient gel electrophoresis, transmission electron microscopy, and dynamic light scattering. The r-HDL were found to be discoidal and in the size range of native HDL. Upon treatment of cholesterol-containing r-HDL with lecithin-cholesterol acyltransferase (LCAT), to form cholesteryl ester, the discoidal r-HDL became spheroidal. The effects of r-HDL morphology and size on HL activity were studied on r-HDL made of palmitoyloleoyl-PC, unesterified cholesterol, cholesteryl ester, and apolipoprotein AI. Spheroidal r-HDL were hydrolyzed at a faster rate than discoidal r-HDL. Protein-poor r-HDL were hydrolyzed by HL at a faster rate than protein rich r-HDL. Unesterified cholesterol had no apparent effect on particle PC hydrolysis. The hydrolysis of different species of PC [dipalmitoyl (DPPC), dioleoyl(DOPC), palmitoylarachidonoyl (PAPC), and palmitoyloleoyl (POPC)] in r-HDL was also investigated. In discoidal r-HDL, we found that POPC >/= DOPC = PAPC/DPPC. However, in LCAT-treated spheroidal r-HDL, POPC = DOPC > PAPC/DPPC. In both discoidal and spheroidal rHDL, DPPC containing r-HDL were not hydrolyzed to a significant extent. Collectively, these studies demonstrate that the physico-chemical properties of particles (such as phospholipid packing and phospholipid acyl composition) play a significant role in hydrolysis of HDL phospholipid by HL and, therefore, in reverse cholesterol transport.     

Modification of the Ehrlich ascites tumor cell nuclear lipids

The fatty acid composition of Ehrilich ascites tumor cell nuclei was differend when the tumor-bearing mice were fed diets rich in either coconut or sunflower oil. When coconut oil was fed, the monoenoic fatty acid content of many of the nuclear lipids was increased and their polyenoic fatty acid content was reduced as compared with the sunflower oil diet. By contrast, only small changes were produced in the saturated fatty acid contents of the nuclear lipids. The nuclear membrane choline phospholipid, ethanolamine phospholipid and combined serine phospholipid plus inositol phospholipid fractions exhibited statistically significant changes in fatty acid composition, but the sphingomyelins were not altered appreciably by dietary lipid modification. The fatty acid composition of the small quantity of phospholipids associated with the chromatin was much more resistant to diet-induced mosification. Except for sphingomyelin, the fatty acid composition of the chromatin phospholipids was different from that of the corresponding nuclear membrane phospholipids, containing much larger amounts of fatty acids having less than 16 carbon atoms. The fatty acid compositons of the nuclear triaclglycerols and cholesterol esters, which were associated almost entirely with the chromatin, were modified by the dietary lipid modifications. There were no changes in the DNA, RNA or lipid content of these nuclei. Therefore, this experimental system can be used to prepare mamalian nuclei that differ appreciably only in their fatty acyl composition.     

Fatty acid composition of myelin isolated from the brain of a patient with cellular deficiency of co-enzyme forms of vitamin B12

Myelin fractionation and subsequent lipid isolation have been carried out on a brain from a patient who suffered from a cellular deficiency of the adenosylcobalamin and methylcobalamin co-enzyme forms of vitamin B12. Examination of the fatty acid composition of choline and ethanolamine glycerophospholipids indicated a relative enrichment of odd-chain fatty acids which were identified by gas-liquid chromatography-mass spectroscopy as C15, C15:1, C17 and C17:1. A mixture of methyl branched C17 fatty acids was also identified. Odd-chain fatty acids accounted for 9.8% of the total fatty acid in the myelin choline phospholipid conpared to control values of 1.2%. The affected brain myelin phospholipids had a lower unsaturated fatty acid content. Examination of the myelin sphingolipids, sphingomyelin, cerebroside and sulfatide, yielded abnormal fatty acid profiles. The sphingomyelin contained only small amounts of C24:1 fatty acid. Both normal and hydroxy fatty acid containing cerebroside and sulfatide had reduced levels of C24 fatty acid. Determination of the relative hydroxy and normal fatty acid content of the galactolipids indicated an abnormally high hydroxy fatty acid level. Abnormal fatty acid profiles of brain cerebral sphingolipids have not been previously described in cases of vitamin B12 deficiency. Whether or not these alterations are characteristic will only be established by estimating sphingolipids in other such cases.     

Taurine accelerates the regression of hypercholesterolemia in stroke-prone spontaneously hypertensive rats

The effects of taurine on the regression of pre-established hypercholesterolemia were examined in stroke-prone spontaneously hypertensive rats (SHRSP). Hypercholesterolemia was induced by feeding a hypercholesterolemic diet to SHRSP for 30 days. Then, the diet was switched to normal chow with or without 3% taurine, and the effects were followed up for another 30 days. During regression serum cholesterol level was rapidly decreased, and was accelerated by taurine. A similar accelerated decrease in cholesterol content by taurine was seen also in tissues including the liver, intestine, and aorta. In the liver, acyl-CoA:cholesterol acyltransferase (ACAT) activity was significantly low in the taurine-supplemented group, parallel with the hepatic cholesteryl ester content. On the other hand, hepatic cholesterol 7 alpha-hydoxylase activity maintained a higher level in the taurine-supplemented group. These results showed that taurine accelerates the regression of hypercholesterolemia, and suggested that this effect is related to the increase in cholesterol catabolism to bile acid through the enhancement of 7 alpha-hydoxylase activity.     

Relationships between serum lipids, platelet membrane fatty acid composition and platelet aggregation in type 2 diabetes mellitus

In order to gain further insight into the mechanism of platelet dysfunction frequently reported in diabetes we investigated circulating fatty acids, lipid composition of platelet membrane and platelet function in Type 2 diabetic patients. In these subjects, percentages of C16 : 1n-7 and C18 : 1n-9 in serum phospholipid fraction and of C16 : 1n-7 in serum cholesterol ester fraction were decreased. Moreover, the content of C20 : 4n-6 in serum cholesterol esters was altered in Type 2 diabetic subjects: C18 : 0 and C20 : 3n-6 were increased but C20 : 4n-6 content was similar to controls. Aggregation in vitro did not differ from controls but aggregation in vivo was increased in Type 2 diabetic subjects. No correlation was observed between metabolic parameters -i.e., HbA1, blood glucose, serum triglycerides and total cholesterol, circulating fatty acids and fatty acid content of platelet membrane. A negative linear correlation was found between aggregation in vivo and C20 : 4n-6 content of platelet membrane. Moreover, a U shaped relationship was observed between platelet aggregation in vitro and C20 : 4n-6 content of platelet membrane suggesting that C20 : 4n-6 level should be tightly controlled otherwise platelet hyperreactivity may occur. These results indicate that despite a normal mean C20 : 4n-6 content in the platelet membrane, regulation of C20 : 4n-6 metabolism is less strictly controlled in Type 2 diabetes mellitus and confirm the importance of arachidonic acid platelet content in the regulation of platelet aggregability.     

In vivo metabolism of alpha-tocopherol in lipoproteins and liver: studies on rabbits in response to acute cholesterol loading

OBJECTIVE: To investigate the transport of alpha-tocopherol in lipoproteins of rabbits under normal diet and under acute loading of cholesterol. DESIGN: Two New Zealand White rabbits were fed 14C-alpha-tocopherol acetate in a single oral dose and the recovery of radiolabel in lipoproteins and plasma was monitored. Low density lipoprotein (LDL) from these animals was obtained and labeled with [3H] cholesteryl ester. Three other rabbits were injected with this double-labeled LDL in the native form; while three other animals received this LDL in the acetylated form. RESULTS: Plasma clearance, liver uptake and levels of radiolabel in high density lipoprotein (HDL) of animals injected with 14C[3H]acetyl LDL were significantly higher than those in animals injected with 14C[3H]native LDL. Larger particles of HDL, rich in apolipoprotein E (apoE) carried significantly higher levels of both labels in rabbits injected with acetylated LDL. CONCLUSION: These results provide evidence for in vivo mechanisms of "reverse alpha-tocopherol transport", analogous to "reverse cholesterol transport".     

The influence of dietary fatty acid composition on N-ethyl-N-nitrosourea-induced mammary tumour incidence in the rat and on the composition of inositol- and ethanolamine-phospholipids of normal and tumour mammary tissue

This study has investigated the influence of dietary fatty acid composition on mammary tumour incidence in N-ethyl-N-nitrosourea (ENU)-treated rats and has compared the susceptibility to dietary fatty acid modification of the membrane phospholipids phosphatidylinositol (PI) and phosphatidylethanolamine (PE) from normal and tumour tissue of rat mammary gland. The incidence of mammary tumours was significantly lower in fish oil--(29%), compared with olive oil--(75%; P < 0.04) but not maize oil--(63%; P < 0.1) fed animals. No differences in PI fatty acid composition were found in normal or tumour tissue between rats fed on maize oil, olive oil or fish oil in diets from weaning. When normal and tumour tissue PI fatty acids were compared, significantly higher amounts of stearic acid (18:0) were found in tumour than normal tissue in rats given olive oil (P < 0.05). A similar trend was found in animals fed on maize oil, although differences between normal and tumour tissue did not reach a level of statistical significance (P < 0.1). In mammary PE, maize oil-fed control animals had significantly higher levels of linoleic acid (18:2n-6) than either olive oil- or fish oil-fed animals (P < 0.05, both cases) and levels of arachidonic acid were also higher in maize oil- compared with fish oil-fed animals (P < 0.05). In tumour-bearing animals no differences in PE fatty acid composition were found between the three dietary groups. When normal and tumour tissue PE fatty acids were compared, significantly lower amounts of linoleic acid (18:2n-6; P < 0.01) and significantly greater amounts of arachidonic acid (20:4n-6; P < 0.05) were found in tumour than normal tissue of rats fed on maize oil. The present study shows that the fatty acid composition of PI from both normal and tumour tissue of the mammary gland is resistant to dietary fatty acid modification. The PE fraction is more susceptible to dietary modification and in this fraction there is evidence of increased conversion of linoleic acid to arachidonic acid in tumour compared with normal tissue. Lower tumour incidence rates in rats given fish oils may in part be due to alteration in prostanoid metabolism secondary to displacement of arachidonic acid by eicosapentaenoic acid, but PE rather than PI would appear to be the most likely locus for diet-induced alteration in prostanoid synthesis in this tissue. Effects of dietary fatty acids other than on the balance of n-6 and n-3 fatty acids, and on prostanoid metabolism, should also be considered. The significance of increased stearic acid content of PI in tumours of olive oil-fed animals and the possible influence of dietary fatty acids on the capacity for stearic acid accumulation requires further study.