Incorporation of dietary trans monounsaturated fatty acids into tissues of Walker 256 tumor-bearing rats (original) (raw)
Related papers
Lipids, 1998
We examined effects of polyunsaturated fatty acids (PUFA), their corresponding hydroperoxy fatty acids (hp-PUFA), as well as various pro-and antioxidants on the growth of tumor cells in culture. When cultured in RPMI 1640 medium, A-427 and WEHI clone 13 cells were both highly sensitive to hydroperoxy docosahexaenoic acid (hp-DHA), but they were far less sensitive in minimum essential medium (MEM). In contrast, A-427 cells were also sensitive to DHA in both culture media, while WEHI clone 13 cells, as well as other cell lines, tested in their respective media, were resistant. The lower sensitivity of the cell lines to hp-DHA in MEM-medium was apparently due to a more rapid reduction of hp-DHA to the corresponding hydroxy-DHA in MEM-medium. Addition of glutathione (GSH) to the culture medium abolished the effects of hp-DHA, but not the effects of DHA, while depletion of intracellular GSH levels by L-buthionine-S,R-sulfoximine strongly enhanced the cytotoxic effect of hp-DHA, but not the cytotoxic effect of DHA. α-Tocopherol protected A-427 cells against the toxic effect of DHA and abolished the induced lipid peroxidation, while it did not protect against the toxic effects of hp-DHA in A-427 or WEHI clone 13 cells. Ascorbic acid reduced the cytotoxic effect of DHA, but potentiated the toxic effect of hp-DHA while selenite essentially abolished the toxicity of both DHA and hp-DHA. These results indicate that sensitivity of tumor cell lines to PUFA and their oxidation products depends on their antioxidant defense mechanisms, as well as culture conditions, and establishes hp-DHA as a major, but probably not the sole, metabolite responsible for cytotoxicity of DHA.
Changes in tissue fatty acid composition in murine malignancy and following anticancer therapy
British journal of cancer, 1992
We studied the mouse NC tumour, a subcutaneously transplanted adenocarcinoma originally of mammary origin. Measurements per g tissue were made of 17 fatty acids (FAs), the combined amounts of n-3, n-6, saturated, unsaturated, and total FAs, and of various FA ratios in the tumour, mammary tissue, spleen, liver and plasma. Compared with mammary tissue from normal mice, tumours of vehicle-treated controls had less of seven of the FAs and more of two FAs. Mice bearing the NC tumour often had changed (usually decreased) amounts of FAs in the 'normal' spleen, liver and plasma, but not in mammary tissue. Treatment with methotrexate (MTX) was studied alone and with indomethacin which can potentiate MTX cytotoxicity. Indomethacin 1.25 mg kg-1 (INDO) increased the amounts of 3/17 tumours FAs and the unsaturated FAs, but reduced 9/17 FAs, the saturated and the unsaturated FAs in 'normal' mammary tissue, and usually had no effect on the FAs of other tissues. MTX 2 or 4 mg kg-1 (...
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2006
Background: Type and composition of dietary fat intake is supposed to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 polyunsaturated fatty acids (PUFA) on oxidative stress (lipidperoxidation) and tumour growth in ductal pancreatic cancer. Methods: Ninety male hamsters were randomized into 6 groups (gr.) (n ¼ 15) and allocated to 3 main dietary categories: gr. 1 and 2 received a standard high fat diet (SHF, rich in n-6 PUFA), while gr. 3 and 4 were fed with a diet containing a mixture of n-3, n-6 and n-9 PUFA (SMOF) and gr. 5 and 6 had free access to a diet rich in n-3 PUFA (FISH-OIL). Gr. 1, 3 and 5 received weekly subcutaneous (s.c.) injections of 10 mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight in order to induce ductal pancreatic adenocarcinoma. Healthy control gr. 2, 4 and 6 were treated with 0.5 ml 0.9% sodium chloride s.c. After 32 weeks all animals were sacrificed. Removed pancreata were weighed and analysed histologically and biochemically. Activities of glutathionperoxidase (GSH-Px), superoxiddismutase (SOD) and levels of lipidperoxidation were measured in samples of pancreatic carcinoma as well as in tumour-free pancreatic tissue. Results: While different diets did not significantly alter the overall incidence of histologically proven pancreatic adenocarcinoma, the number of macroscopically visible tumours was decreased in the FISH-OIL-gr. Conclusion: Different diets did not significantly influence the incidence of histologically proven pancreatic adenocarcinoma. However, administration of a diet rich in n-3 PUFA (FISH-OIL) resulted in a decrease of macroscopically visible tumours, thus indicating its beneficial effects in respect to attenuation of tumour growth.
The Journal of Nutritional Biochemistry, 2001
The aim of this study was to analyze the effects of a polyunsaturated n-6 high-fat diet on rat DMBA-induced breast cancer at different stages of the carcinogenesis and to investigate if changes in the tumor fatty acid composition are one of the mechanisms by which dietary lipids could exert their effects. 14 fatty acids were evaluated in 6 lipid fractions. The results firstly showed that this high-fat diet stimulated the malignant mammary tumor growth, mainly all in the promotion group. The tumor lipid analysis indicated: 1) that each lipid fraction presented distinct major fatty acids (Ͼ5%) which were not the most abundant in the diet, except in the case of the triacylglicerides, suggesting the different resistance to dietary fatty acid modification of the tumor lipid fractions; 2) a higher arachidonic acid content in the fractions with less linoleic acid, above all in phospholipids, particularly in the phosphatidylethanolamine, indicating a different efficiency of conversion; 3) the three most abundant fatty acids in the dietary lipid (18:2n-6, 18:1n-9 and 16:0) were those which essentially displayed the differences between groups; thus, the high-fat diet changed the tumor lipid profile, increasing the 18:2n-6 relative content and decreasing that of the 18:1n-9; differences were significant in phosphatidylcholine, free fatty acids and triacylglycerides. Any change was obtained in the phosphatidylinositol. The greatest number of differences was found in the promotion group. Taken as a whole, our results suggest the different roles of lipid fractions in breast cancer cells and an association between cancer malignancy and the content of linoleic and oleic acids.
Journal of Nutrition, 2000
We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the Apc Min/ϩ mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of ␣-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or ␥-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the ⌬6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of Apc Min/ϩ mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by ϳ50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P ϭ 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA-and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.
Nutrition and Cancer, 2000
To investigate whether the oxidative status of an 18:3(n-3) polyunsaturated fatty acid (PUFA)-enriched diet could modulate the growth of chemically induced rat mammary tumors, three independent experiments were performed. Experiments I and II examined the variation of tumor growth by addition of antioxidant (vitamin E) or a prooxidant system (sodium ascorbate/2-methyl-1,4-naphthoquinone) to a 15% linseed oil diet rich in 18:3(n-3). Experiment III addressed the role of PUFA in the tumor growth modulation by vitamin E. For this purpose, we compared the effect of vitamin E in 15% fat diets containing a high level of 18:3(n-3) (linseed oil, high-PUFA diet) or devoid of 18:3(n-3) (hydrogenated palm/sunflower oil, low-PUFA diet). In Experiments I-III, tumor growth increased in the presence of vitamin E compared with control (without vitamin E). Furthermore, it decreased when prooxidant was added. In contrast, no difference was observed when the diet was low in PUFA, suggesting that sensitivity of PUFA to peroxidation may interfere with tumor growth. This observation was supported by growth kinetic parameter analysis, which indicated that tumor growth resulted from variations in cell loss but not from changes in cell proliferation. These data show that, in vivo, PUFA effects on tumor growth are highly dependent on diet oxidative status.
Prostaglandins Leukotrienes and Essential Fatty Acids, 1997
The effect of dietary polyunsaturated fatty acids (PUFAs) on whole body-induced tumorigenesis was assayed in mice fed on essential fatty acid sufficient (EFAS) or essential fatty acid deficient (EFAD) diets following cobalt-60 irradiation. Four groups of mice were maintained, one on a control stock diet and three on experimental diets: a) without added fat (fat free, FF); b) containing 5% olein (O), rich in n-9; and c) containing 5% corn oil, rich in n-6 EFA (CO). Only mice fed on FF or O diets showed clinical and biochemical signs of EFAD. Total incidence of tumors showed an increase in FF (P < 0.02) and O (P < 0.03) mice. Tumors developed mostly in the liver in each of the EFAD groups (P < 0.001). Slight promoting activity on lung tumorigenesis was recorded in the CO group when this parameter was compared in EFAD and EFA sufficient mice. It may be concluded that, when a tumor initiator injures the body as a whole, EFAD, achieved either through a fat-free or an oleic-supplemented diet, behaves as a general promoting condition for tumorigenesis. The borderline tumorigenic effect of n-6 corn oil on the lungs suggests that this effect, when present, is target specific.