Toxicity of fatty acids on ECV-304 endothelial cells

The effects of stearic (saturated) or oleic (monounsaturated) acids and their combination with ω-3 and ω-6 polyunsaturated fatty acids (PUFA) on death of endothelial cells (ECV-304 cell line) were investigated. We examined: loss of plasma membrane integrity, DNA fragmentation, accumulation of neutral lipids (NL) and release of reactive oxygen species (ROS). The fatty acids studied were: stearic (SA), oleic (OA), docosahexaenoic (DHA), eicosapentaenoic (EPA), linoleic (LA) and gamma-linolenic (γA) acids. SA at 150 μM induced cell death, did not lead to accumulation of NL and raised the release of ROS. ω-3 PUFA decreased ROS production, increased NL content but did not protect against ECV-304 cell death induced by SA. ω-6 PUFA inhibited SA-induced cell death, increased NL content and decreased ROS production. OA caused cell death but did not increase NL content and ROS production even at 300 μM. ω-3 and ω-6 FA associated with OA further increased cell death with no change in ROS production and NL content. Concluding, ω-6 PUFA had a greater protective effect than ω-3 PUFA on the deleterious effects caused by SA whereas OA had low cytotoxicity but, when associated with PUFA, presented marked toxic effects on ECV-304 endothelial cells.     

Effect of Sargassum thunbergii on ROS mediated oxidative damage and identification of polyunsaturated fatty acid components

In this study, we examined protective effect of Sargassum thunbergii on reactive oxygen species (ROS) mediated oxidative stress in cellular systems. In addition, polyunsaturated fatty acids from S. thunbergii were identified and quantified by gas chromatography mass spectroscopy. Intracellular ROS levels were measured using a oxidation sensitive dye, 2′,7′-dichlorofluorescein diacetate (DCFH-DA). Treatment with S. thunbergii significantly reduced intracellular ROS mediated cell damage and inhibited myeloperoxidase (MPO) activity assessed in tumor necrosis factor-α (TNF-α) stimulated human monocytic leukemia in a concentration-dependent manner. Moreover, antioxidative mechanisms by S. thunbergii were evaluated by measuring the expression levels of antioxidative enzymes such as superoxide dismutase (SOD-1), catalase, glutathione peroxidase and glutathione reductase. SOD-1 and glutathione reductase were up-regulated by S. thunbergii. Furthermore, S. thunbergii contains polyunsaturated fatty acids such as arachidonic acid, arachidic acid, palmitic acid, elaidic acid, linoleic acid, stearic acid and cis-5,8,11,14,17-eicosanoic acid. Therefore, these results suggested that S. thunbergii has nutraceutical effectiveness in prevention of ROS-induced tissue damage and potential natural antioxidant related to oxidative stress, which can be traceable to polyunsaturated fatty acids contained in S. thunbergii.     

Free radical scavenging and antiatherogenic activities of Sesamum indicum seed extracts in chemical and biological model systems

An emerging consensus underscores the importance of oxidative events in vascular disease including excess production of reactive oxygen/nitrogen species (ROS/RNS), in addition to lipoprotein oxidation. Sesamum indicum has long been used extensively as a traditional food. The aim of present study was to evaluate antioxidant action of aqueous and ethanolic seed extracts from S. indicum using various in vitro ROS/RNS generated chemical and biological models. Results demonstrated that the graded-dose (25–1000 μg/ml) of aqueous and ethanolic extracts markedly scavenged the nitric oxide, superoxide, hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, showed metal chelating ability as well as reducing capacity in Fe³⁺/ferricyanide complex and ferric reducing antioxidant power assays. In biological models, both extracts were found to inhibit metal-induced lipid peroxidation in mitochondrial fractions, human serum and LDL oxidation models. In lipoprotein kinetics study, both extracts significantly (P < 0.05) increased lag phase time along with reduced oxidation rate and conjugated dienes production. Ethanolic extract of S. indicum showed higher amounts of total polyphenol and flavonoid content as compared to their counterpart. The IC₅₀ values of both extracts were compared with respective antioxidant standards. Overall, ethanolic extract of S. indicum possess strong antioxidant capacity and offering effective protection against LDL oxidation susceptibility.     

Impact of the carotenoid astaxanthin on phagocytic capacity and ROS/RNS production of human neutrophils treated with free fatty acids and high glucose

BackgroundThe purpose of the present study was to evaluate the effect of carotenoid astaxanthin (ASTA) on human neutrophils treated with high glucose and free fatty acids (FFA) on the phagocytic capacity and reactive oxygen/nitrogen species production.MethodsThe following parameters were evaluated: phagocytic capacity of neutrophils by using zymosan particles, intracellular and extracellular superoxide anion (lucigenin and DHE probes), hydrogen peroxide (H₂O₂ — phenol red), nitric oxide (Griess reagent) production, and maximal activity of G6PDH.ResultsThere was a decreased phagocytic capacity of human neutrophils treated with high glucose (30 mM) or FFA (0.1 mM) and a partial restoring of the phagocytic capacity after ASTA-treatment was observed. ROS and RNS production was increased in neutrophils due to both high glucose and FFA. This increase in ROS/RNS production was also partially prevented by ASTA treatment. Both glucose and FFA increased the G6PDH activity. We show that ASTA provides a modest improvement of cellular functions after cells have been treated with high glucose and FFA.ConclusionsIn summary, this study showed that both high glucose and a mixture of FFA are potent inducers of ROS/RNS production on neutrophils as observed by higher levels of superoxide anion, hydrogen peroxide and NO production. Also, these metabolites decrease the phagocytic capacity of neutrophils and increase the G6PDH activity. Overall, ASTA-treatment was able to reduce partially ROS/RNS production by reducing the availability of NADPH and recover phagocytic capacity of neutrophils.     

Impact of the carotenoid astaxanthin on phagocytic capacity and ROS/RNS production of human neutrophils treated with free fatty acids and high glucose

Background

The purpose of the present study was to evaluate the effect of carotenoid astaxanthin (ASTA) on human neutrophils treated with high glucose and free fatty acids (FFA) on the phagocytic capacity and reactive oxygen/nitrogen species production.

Methods

The following parameters were evaluated: phagocytic capacity of neutrophils by using zymosan particles, intracellular and extracellular superoxide anion (lucigenin and DHE probes), hydrogen peroxide (H₂O₂ — phenol red), nitric oxide (Griess reagent) production, and maximal activity of G6PDH.

Results

There was a decreased phagocytic capacity of human neutrophils treated with high glucose (30 mM) or FFA (0.1 mM) and a partial restoring of the phagocytic capacity after ASTA-treatment was observed. ROS and RNS production was increased in neutrophils due to both high glucose and FFA. This increase in ROS/RNS production was also partially prevented by ASTA treatment. Both glucose and FFA increased the G6PDH activity. We show that ASTA provides a modest improvement of cellular functions after cells have been treated with high glucose and FFA.

Conclusions

In summary, this study showed that both high glucose and a mixture of FFA are potent inducers of ROS/RNS production on neutrophils as observed by higher levels of superoxide anion, hydrogen peroxide and NO production. Also, these metabolites decrease the phagocytic capacity of neutrophils and increase the G6PDH activity. Overall, ASTA-treatment was able to reduce partially ROS/RNS production by reducing the availability of NADPH and recover phagocytic capacity of neutrophils.     

Induction of apoptosis and modulation of production of reactive oxygen species in human endothelial cells by diphenyleneiodonium

Diphenyleneiodonium (DPI) inhibits activity of flavoenzymes like NADPH oxidase, the major source of superoxide anion in cardiovascular system, but affects also other oxidoreductases. Contradictory data have been published concerning the effect of diphenyleneiodonium on the production of reactive oxygen species in cells, both inhibitory and stimulatory action of DPI being reported. We have examined the effect of DPI on the cellular production of reactive oxygen and nitrogen species (ROS/RNS) and on the proliferation and apoptosis of human vascular endothelial cells. We found increased oxidation of ROS-sensitive probes (dihydrorhodamine 123 and 2',7'-dichlorodihydrofluorescein diacetate) when DPI (20 microM-100 microM) was present in the treated cells. However, oxidation of the fluorogenic probes was inhibited if DPI (20 microM-100 microM) was removed from the reaction medium after cell preincubation. These results suggest an artifactual oxidation of the fluorogenic probes by DPI or its metabolites. A similar pattern of influence of DPI on the production of NO (measured with 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate) was observed. Modulation of generation of reactive oxygen and nitrogen species in DPI-treated cells influenced the nitration of tyrosine residues of cellular proteins, estimated by Western blotting. Decreased level of nitration generally paralleled the lowered production of ROS. A decreased 3-(4,5-dimethylthiazolyl)-3-3(4-sulphophenyl) tetrazolium (MTT) reducing activity of cells for was observed immediately after 1h treatment of human endothelial cells with DPI (1 microM-100 microM), in spite of lack of changes in cell viability estimated by other methods. These results point to a next limitation of MTT in estimation of viability of cells treated with oxidoreductase inhibitors. DPI inhibited the proliferation of HUVECs as well as immortalized cell line HUVEC-ST, as assessed by acid phosphatase activity test and measurement of total nucleic acid content. Proapoptotic action of DPI was observed 12 h after incubation with this compound.     

Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging

The overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a common underlying mechanism of many neuropathologies, as they have been shown to damage various cellular components, including proteins, lipids and DNA. Free radicals, especially superoxide (O(2)*-), and non-radicals, such as hydrogen peroxide (H(2)O(2)), can be generated in quantities large enough to overwhelm endogenous protective enzyme systems, such as superoxide dismutase (SOD) and reduced glutathione (GSH). Here we review the mechanisms of ROS and RNS production, and their roles in ischemia, traumatic brain injury and aging. In particular, we discuss several acute and chronic pharmacological therapies that have been extensively studied in order to reduce ROS/RNS loads in cells and the subsequent oxidative stress, so-called "free-radical scavengers." Although the overall aim has been to counteract the detrimental effects of ROS/RNS in these pathologies, success has been limited, especially in human clinical studies. This review highlights some of the recent successes and failures in animal and human studies by attempting to link a compound's chemical structure with its efficacy as a free radical scavenger. In particular, we demonstrate how antioxidants derived from natural products, as well as long-term dietary alterations, may prove to be effective scavengers of ROS and RNS.     

Oxidative stress,polyunsaturated fatty acidsderived oxidation products and bisretinoids as potential inducers of CNS diseases: focus on age-related macular degeneration

Many pathologies of the central nervous system (CNS) originate from excess of reactive free radicals, notably reactive oxygen species (ROS), and oxidative stress. A phenomenon which usually runs in parallel with oxidative stress is unsaturated lipid peroxidation, which, via a chain reaction, contributes to the progression of disbalanced redox homeostasis. Among long-chain (LC) polyunsaturated fatty acids (PUFAs) abundantly occurring in the CNS, docosahexaenoic acid (DHA), a member of ω-3 LC-PUFAs, deserves special attention, as it is avidly retained and uniquely concentrated in the nervous system, particularly in retinal photoreceptors and synaptic membranes; owing to the presence of the six double bonds between carbon atoms in its polyene chain (C=C), DHA is exquisitely sensitive to oxidative damage. In addition to oxidative stress and LC-PUFAs peroxidation, other stress-related mechanisms may also contribute to the development of various CNS malfunctions, and a good example of such mechanisms is the process of lipofuscin formation occurring particularly in the retina, an integral part of the CNS. The retinal lipofuscin is formed and accumulated by the retinal pigment epithelial (RPE) cells as a consequence of both visual process taking place in photoreceptor-RPE functional complex and metabolic insufficiency of RPE lysosomal compartment. Among various retinal lipofuscin constituents, bisretinoids, originating from all-trans retinal substrate – a photometabolite of visual pigment cofactor 11-cis-retinal (responsible for photon capturing), are endowed with cytotoxic and complement-activating potential which increases upon illumination and oxidation. This survey deals with oxidative stress, PUFAs (especially DHA) peroxidation products of carboxyalkylpyrrole type and bisretinoids as potential inducers of the CNS pathology. A focus is put on vision-threatening disease, i.e., age-related macular degeneration (AMD), as an example of the CNS disorder whose pathogenesis has strong background in both oxidative stress and lipid peroxidation products.     

Effects of culture duration on hydrogen peroxide-induced hepatocyte toxicity

The effects of culture duration on primary cultured mouse hepatocyte antioxidant levels (superoxide dismutase, catalase, glutathione peroxidase, vitamin E, and glutathione) and susceptibility to glucose oxidase (GO)- and hydrogen peroxide (H2O2)-induced cell killing and lipid peroxidation were examined. Membrane fatty acid composition was also evaluated. Adult male B6C3F1/CrlBR mouse hepatocytes were isolated by collagenase perfusion of the liver and cultured on 60-mm plastic dishes in Leibovitz's L-15 medium supplemented with glucose (1 mg/ml), dexamethasone (1 microM), fetal bovine serum (10%, v/v), and gentamicin sulfate (50 micrograms/ml) for 0 hr (freshly isolated cells) to 96 hr. Hepatocyte toxicity (determined by lactate dehydrogenase release and lipid peroxidation) after a 2-hr exposure to GO (0.8-80 micrograms/ml) or H2O2 (1-5 mM) decreased with increased time in culture. This decreased hepatocyte sensitivity to GO and H2O2 toxicity was not related to antioxidant enzyme activity since superoxide dismutase, catalase, and glutathione peroxidase declined during the 96-hr culture period. In contrast, glutathione and vitamin E levels in the cultured hepatocytes rose to 274.9 +/- 8.3% and 220.6 +/- 18.6% of the levels in freshly isolated cells (129.6 +/- 11.5 nmol and 0.10 +/- 0.01 nmol per 10(6) hepatocytes, respectively). The percentage of polyunsaturated fatty acids in hepatocyte phospholipids and triglycerides decreased with culture duration while the percentage of oleic acid increased in esterified and free fatty acid pools after 2 hr in culture. Total fatty acids were not affected by time in culture. These results suggest that the decreased hepatocyte susceptibility to the toxic effects of hydrogen peroxide may have been due to elevations in cellular GSH and vitamin E levels and decreases in membrane polyunsaturated fatty acids. The data also indicate that hepatocytes in primary culture undergo changes in antioxidant levels and fatty acid composition that may affect free radical toxicity at different times in culture.     

Chemical characterisation of three haemolytic compounds from the microalgal species Fibrocapsa japonica (Raphidophyceae).

The molecular structures of the three main haemolytic compounds (Fj1, Fj2 and Fj3) isolated from the ichthyotoxic microalgal species Fibrocapsa japonica have been investigated by NMR, LC-ESI-MS, ESI-MS-MS, IR, GC-MS and GC-HRMS methods. They are polyunsaturated fatty acids which we identified as: 6,9,12,15-octadecatetraenoic acid (OTA, C18:4omega3), 5,8,11,14,17-eicosapentaenoic acid (EPA, C20:5omega3) and 5,8,11,14-eicosatetraenoic acid (arachidonic acid AA, C20:4omega6). The identity of the latter two was confirmed on the basis of commercial standards (C20:5omega3 and C20:4omega6). Both displayed the same spectroscopic and chromatographic characteristics as Fj2 and Fj3 and had a similar strong haemolytic effect. We propose that when F. japonica cells accumulate in fish gills during blooms these compounds could be the cause of icthyotoxicity.     

Dietary omega 3 polyunsaturated fatty acids augment endothelium-dependent relaxation to bradykinin in coronary microvessels of the pig.

1. The effects of chronic dietary supplementation with omega 3 polyunsaturated fatty acids on endothelium-dependent relaxations were examined in isolated coronary microvessels of the pig. 2. Animals were maintained for four weeks with or without dietary supplementation of purified eicosapentaenoic acid (3.5 g daily) and docosahexaenoic acid (1.5 g daily). Fatty acid profiles of plasma lipids showed that only the fraction of eicosapentaenoic acid increased by the treatment, together with a decrease of that of arachidonic acid. 3. In the treated group, endothelium-dependent relaxations to bradykinin were significantly augmented, while contractions to acetylcholine or relaxations to nitroprusside were unaltered. 4. These results indicate that dietary omega 3 polyunsaturated fatty acids (mainly eicosapentaenoic acid) augment endothelium-dependent relaxations in coronary microvessels of the pig, without changing the ability of vascular smooth muscle to contract or relax.     

Exacerbation of alcohol-induced oxidative stress in rats by polyunsaturated Fatty acids and iron load

The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron.     

Safety assessment of SDA soybean oil: Results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats

Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5–4%) and in nutraceuticals (echium, borage oil). Genes for Δ6, Δ15 desaturases were introduced into soybeans that convert linoleic and α-linolenic acid to SDA (15–30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3 g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development.     

Unsaturated fatty acids and pain

Fatty acids, which are the essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a range of biological phenomena. Recently, an increasing number of physiologic and pharmacologic reports on fatty acids have improved our understanding of the association of fatty acids with certain diseases. It has also become apparent that functional properties of fatty acids are modulated by factors such as the amount of individual fatty acid intake and their distribution among organs. Recently, the functional relationship between polyunsaturated fatty acids and pain has been the focus of many studies. Both basic and clinical studies have shown that a dietary intake of n-3 series polyunsaturated fatty acids results in a reduction in the pain associated with rheumatoid arthritis, dysmenorrhea, inflammatory bowl disease, and neuropathy. In addition, levels of n-6 series polyunsaturated fatty acids are high in patients with chronic pain. These results indicate that polyunsaturated fatty acids play a vital role in pain regulation. In this review, we summarize a number of basic and clinical studies on polyunsaturated fatty acids and their association with pain.     

火麻仁油与海藻油混合物对氧化性低密度脂蛋白诱导的内皮细胞损伤的分子保护机制研究

目的：探讨由植物来源的多不饱和脂肪酸火麻仁油与海藻油混合而成的混合物（简称AH）对氧化性低密度脂蛋白（ox-LDL）诱导的内皮细胞损伤的保护作用。方法：用ox-LDL刺激人脐静脉内皮细胞株（HUVEC-12）建立内皮细胞损伤模型，药物干预后检测细胞内NO含量，流式细胞仪检测ROS变化，TUNEL法检测细胞凋亡，RT-PCR方法检测IL-6、TNF-α、NF-κB、pAMPK、SIRT1的基因表达水平，Western-Blot方法检测P-IκB、pAMPK、SIRT1蛋白表达水平。结果：与模型组相比，多不饱和脂肪酸混合物AH可以显著减少细胞NO合成，减少ROS生成，抑制细胞凋亡，降低IL-6、TNF-α、NF-κB水平，增加pAMPK、SIRT1水平。结论：AH能够通过降低内皮炎症因子来对抗ox-LDL诱导的内皮损伤，其作用机制可能与AMPK/SIRT1/NF-κB信号通路有关。     

Oxidative stress as a regulator of murine atherosclerosis

Altered cellular production of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) is a ubiquitous feature of human disease. Vascular oxidative stress is a unifying area of research in atherosclerosis and aging. While elevated levels of ROS, especially oxygen radicals (O2-) and hydrogen peroxide (H2O2), induce cellular apoptosis, low levels play an important role in cell signaling [1,2]. Reactive species from a variety of sources further play an important role in plaque disruption partly through lipid oxidation, low-density lipoprotein oxidation nitration, and signaling [3-6].     

Chronic obstructive pulmonary disease and oxidative stress

The respiratory tract as the main entrance for various inhalative substances has great potential to generate reactive species directly or indirectly in excess. Thus, heavy smokers are at high risk for development, impairment and failed response to treatment of chronic obstructive pulmonary disease (COPD). The article is an update regarding the influence of reactive oxygen (ROS) and nitrogen (RNS) species on COPD; however, we do not intend to describe ROS and RNS actions on the entire lung tissue. Here, we focus on the airways, because in human most of the described effects of ROS and RNS species are measured on respiratory epithelial cells obtained by bronchoscopy. ROS and RNS species are physiological compounds in cells and risk factors for several respiratory diseases. In general, both kinds of species are thermodynamically stabile, but their reaction behaviors in cellular environments are very different. For example, the life times of the superoxide anion radical range from micro/milliseconds up to minutes and even hours in in-vitro model systems. Oxidative stress by cigarette smoke was investigated in detail by the authors of this article. In addition, original studies by the authors on the amount of fine particulate matter and trace elements in lung biopsies after defined inhalation indicate a distortion of the equilibrium between oxidants and antioxidants. We also try to present some modern views with respect to genomic medicine for future therapeutic perspectives, although this is an upcoming sector of COPD therapy.     

Protection of synaptosomal polyunsaturated fatty acids from by extract of Ginkgo biloba-EGb 761

Previous studies have demonstrated that ascorbic acid associated with ferrous ions induced deleterious effects on several targets or functions of striatal dopaminergic nerve endings, which were prevented by the Ginkgo biloba extract EGb 761. The present study attempted to assess whether a peroxidation of polyunsaturated fatty acids of their membranes could be associated with (or even responsible for) these alterations. Synaptosomes were prepared from mice striata. Their 1 h incubation with ascorbic acid (0.1 mM) resulted in a marked increase (+300%) of thiobarbituric acid reactive substances, that roughly are considered to correspond to the malondialydehyde level. Under these conditions the level of polyunsaturated fatty acids, measured by gas chromatography, decreased by -23% whereas the level of saturated fatty acids was not modified. Both the increase in thiobarbituric acid reactive substances and the decrease in polyunsaturated fatty acids were prevented by EGb 761 (10 micro g/ml). Similarly, the increase of TBARS was prevented by the vitamin E analogue trolox C (0.1mM) as well as by the ferrous ions chelating agent desferrioxamine (0.1mM). These data suggest that the polyunsaturated fatty acids peroxidation could be the origin of previously reported synaptosomal alterations induced by ascorbic acid/Fe(2 +).     

Differential influence of pre- and post-delta-6-desaturation n6 polyunsaturated fatty acids on fibroblasts in culture, compared to n9 monounsaturated and n3 polyunsaturated fatty acids

There is now considerable evidence that polyunsaturated fatty acids (PUFA) are effective in vitro at limiting the growth of cancer cells while not affecting normal cells to the same extent. Twenty carbon PUFA, especially of the n3 series, have been shown to be particularly potent; while the eighteen carbon n6 fatty acid, linoleic acid has been implicated in growth stimulation of breast cancer. We report here on the comparative effects of a range of eighteen and twenty carbon fatty acids of varying degrees of unsaturation on normal and transformed fibroblasts in culture. All moieties of the n3 series showed high potency in limiting transformed cell growth, while cis and trans monounsaturates and pre-delta-6-desaturation n6 polyunsaturates induced a mixed response, even inducing comparative growth stimulation with some fatty acid concentrations.