The effect of dietary zinc - and polyphenols intake on DMBA-induced mammary tumorigenesis in rats

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to investigate the effect of dietary supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein, on the effectiveness of chemically induced mammary cancer and the changes in the content of selected elements (Zn, Cu, Mg, Fe, Ca) in tumors as compared with normal tissue of the mammary gland.</p> <p>Methods</p> <p>Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet and DMBA (7,12-dimethyl-1,2- benz[a]anthracene), were treated with zinc ions (Zn) or zinc ions + resveratrol (Zn + resveratrol) or zinc ions + genistein (Zn + genistein) via gavage for a period from 40 days until 20 weeks of age. The ICP-OES (inductively coupled plasma optical emission spectrometry) technique was used to analyze the following elements: magnesium, iron, zinc and calcium. Copper content in samples was estimated in an atomic absorption spectrophotometer.</p> <p>Results</p> <p>Regardless of the diet (standard; Zn; Zn + resveratrol; Zn + genistein), DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn + resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. On the basis of quantitative analysis of selected elements we found - irrespectively of the diet applied - great accumulation of copper and iron, which are strongly prooxidative, with a simultaneous considerable decrease of the magnesium content in DMBA-induced mammary tumors. The combination of zinc supplementation with resveratrol resulted in particularly large differences in the amount of the investigated elements in tumors as compared with their content in normal tissue.</p> <p>Conclusions</p> <p>Diet supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein had no effect on the decreased copper level in tumor tissue and inhibited mammary carcinogenesis in the rat. Irrespectively of the applied diet, the development of the neoplastic process in rats resulted in changes of the iron and magnesium content in the cancerous tissue in comparison with the healthy mammary tissue. The application of combined diet supplementation with zinc ions and resveratrol considerably promoted the rate of carcinogenesis and increased the number of DMBA-induced mammary tumors.</p

Active Compounds in Fruits and Inflammation in the Body

Inflammation plays an important role in the pathogenesis of many diseases, including cardiovascular diseases, atherosclerosis, diabetes, asthma, and cancer. An appropriate diet and the active compounds contained in it can affect various stages of the inflammatory process and significantly affect the course of inflammatory diseases. Recent reports indicate that polyphenolic acids, vitamins, minerals, and other components of fruits may exhibit activity stimulating an anti-inflammatory response, which may be of importance in maintaining health and reducing the risk of disease. The article presents the latest data on the chemical composition of fruits and the health benefits arising from their anti-inflammatory and antioxidant effects. The chemical composition of fruits determines their anti-inflammatory and antioxidant properties, but the mechanisms of action are not fully understood

Laser Ablation ICP-MS Analysis of Chemically Different Regions of Rat Prostate Gland with Implanted Cancer Cells

The comparison of tissues analyzed by LA-ICP-MS is challenging in many aspects, both medical and mathematical. The concept of distinguishing regions of interest (ROIs) was proposed in the literature, allowing for data reduction and targeted comparative analysis. ROIs can be drawn before any analysis, by indicating the anatomical parts of tissue, or after the first step of analysis, by using elemental distribution maps and characteristic regions of enrichment in selected elements. A simple method for identifying different regions, without the manual extraction of image fragments, is highly needed in biological experiments, where large groups of individuals (with samples taken from each of them) is very common. In the present study, two ROIs were distinguished: (1) tissue-rich in fat (and tissue-poor in water); and (2) tissue-rich in water (and tissue-poor in fat). ROIs were extracted mathematically, using an algorithm based on the relationship between 13C and 23Na signal intensities. A cut-off point was indicated in the point of the simultaneous decrease in 13C and increase in 23Na signal intensity. Separate analyses of chemically different ROIs allow for targeted comparison, which is a great advantage of laser ablation over liquid introductions to ICP-MS. In the present experiment, tissues were provided from animals with implanted prostate cancer cells as well as supplemented with mineral compounds particularly important both for prostate gland functions (Zn and Se) and neoplastic processes (Ca, Fe, and Cu). One of the goals was to try to determine whether dietary supplementation qualitatively and quantitatively affects the mineral composition of the prostate gland

The importance of folic acid for the health of the human body

A well-balanced diet is undoubtedly a key factor to maintain your body's normal state of health. A deficiency or excess of any nutrient can cause negative effects on human health. Folic acid is one of the elements of the diet, which is often supplied in insufficient quantities. This vitamin and its derivatives participate in the metabolism of amino acids and nucleic acids. Therefore, it is necessary for the proper functioning of the body's cells and for maintaining homeostasis, especially of the nervous, circulatory and cardiovascular systems. The biological activity of folic acid and its derivatives essentially affects the metabolism of important amino acids, such as methionine, homocysteine, serine, glycine, pyrimidine and purine synthesis and DNA methylation. The synthetic form of folic acid (most oxidized), which can be found in fortified foods, dietary supplements or pharmaceuticals, does not show biological activity. It is transformed in a series of reactions with the participation of many enzymes to form folates, which differ in the number of glutamic acid residues and the degree of oxidation. The actively biological form is reduced folate (L-5-MTHF), which is transported together with the blood to cells where it undergoes biological processes important for our health. The MTHFR gene, coding for the enzyme protein of the same name - methylene tetrahydrofolate reductase, is located on chromosome 1 at the 1p36.3 locus. This protein is responsible for the catalysis of the enzymatic reaction, which is the reduction of 5,10-methylenetetrahydrofolate to L-5-methyltetrahydrofolate, i.e. the active form of folate. This form is necessary in the process of homocysteine degradation, in the aftermath remethylation to methionine. This protein is responsible for the catalysis of the enzymatic reaction, which is the reduction of 5,10-methylenetetrahydrofolate to L-5-methyltetrahydrofolate, i.e. the active form of folate. This form is necessary in the process of homocysteine degradation, in the aftermath remethylation to methionine. However, according to available literature, mutation of the MTHFR 677C> T gene occurs in even 53% of the population. Among carriers of the TT genotype, it can cause about 70% reduction of MTHFR reductase activity. It is especially dangerous for people who do not provide adequate amounts of folic acid along with their diet and for those who need a high amount of this vitamin, e.g. due to taking medications that reduce its absorption, i.e. metformin or oral contraceptives. Many people metabolize folic acid on insufficient levels. For medical reasons, not the mutation itself is a problem, but too low the folate levels. In recent years, there is more and more discussion about the active form of folic acid and the possibility of effective supplementation with metapholine, which is a combination of calcium with L-5-MTHFR. It is a natural and reduced form of folate, which hydrolized and then transforms into L-5-MTHFR. Metapholine, in comparison to folic acid, is not reduced to be incorporated into metabolic processes in the cell, which is catalyzed by DHFR and MTHFR enzymes. In addition, the absorption of the active form of folic acid is faster because some metabolic pathways are missed. This is particularly important for people who have a MTHFR gene mutation homozygous with 665C> T and / or 1298A> C polymorphism and a mutation of the DHFR gene with 458A> T polymorphism. Numerous clinical studies have confirmed the efficacy and safety of the active form of folic acid. In a study by Houghton et al., which was conducted among pregnant Canadian women, L-5-MTHFR was shown to be at least as effective in lowering homocysteine levels as folic acid supplementation. In addition, the active form of folic acid was more effective at storing folate in erythrocytes. In a study conducted by Lamers et al. on 135 women after a period of 24 weeks, L-5MTHR was shown to be a suitable alternative in reducing plasma homocysteine levels compared to folic acid and placebo. In addition, Bentley et al. analyzed the results of 112 pregnant women from the USA. Patients were assigned to two groups in which each took vitamin B12. In addition, in one of them women supplemented with L-5-MTHFR, and in the other - folic acid. The results showed that patients who supplemented the active form of folic acid not only had higher hemoglobin levels, but also less often had anemia. When analyzing clinical trials of patients with the MTHFR mutation, the same trend was observed. Metafoline increased plasma folate levels and decreased homocysteine levels. In one study on German women, there was a decrease in homocysteine levels and an increase in folate levels in both plasma and red blood cells in patients who supplemented the active form of folic acid. In another study involving Swiss patients with the current 677CC MTHFR or 677TT MTHFR mutation, it was demonstrated that using L-5-MTHFR significantly reduces homocysteine levels compared to folic acid. It is also worth mentioning that Prinz-Langenhol et al. in a study on women with the 677CC and 677TT mutations proved that the active form of folic acid has a better effect on increasing folate levels than folate. It is also worth mentioning that folic acid at high doses can mask ailments or even diseases caused by vitamin B12 deficiency. In addition, folic acid administered at high doses in patients with the MTHFR mutation is not reduced to an oxidized, inactive form and is not properly transported to plasma. Non-metabolised folic acid can be dangerous to the human body and contribute to the development of cancer. Supplementation, in particular the active form of folic acid, should be considered by patients who are carriers of the MTHFR or DHFR mutation. In addition, the use of stimulants such as alcohol or nicotine also negatively affects the absorption of this vitamin. Taking some medications weakens the absorption of folic acid - these include folic acid antagonists, anti-tuberculosis drugs, hormonal oral contraceptives, nonsteroidal anti-inflammatory drugs or metformin widely used. Folic acid is necessary for the proper functioning of the human body and its deficiency may induce various disease processes in the body, which include: the formation of neural tube defects, disorders in the nervous system, megaloblastic anemia, a negative effect on the functioning of the cardiovascular system and the development of atherosclerosis and cancer. More and more people have anemia, including megaloblastic anemia, which is characterized by abnormal nucleic acid synthesis. The consequence of too low folate levels is impaired red blood cell production, an increase in their volume, and premature death. Extremely dangerous is megaloblastic anemia, the so-called malignant anemia in pregnant women, as it can lead to serious complications such as hemorrhage, infection, and even intrauterine fetal death. A significant influence of folic acid on the functioning of the nervous system has been proven in many clinical studies. This vitamin is involved in the formation of important neurotransmitters such as: adrenaline, dopamine and noradrenaline, therefore its deficiency may lead to the development of neuropsychiatric disorders (dementia, epilepsy, depression and psychosis). These disorders are often caused by high levels of homocysteine, which is not properly metabolized to methionine due to folate deficiency. An excess of homocysteine, as a consequence, leads to atherosclerosis in the cerebral arteries and, as a result of insufficient blood supply, transient ischaemic attack occur, which can contribute to the development of dementia or Alzheimer's disease. Nutritional observations indicate that eating fresh vegetables rich in folic acid protects against the formation of some cancers, e.g. large intestine, breast, ovary, uterus, lungs, pancreas. Deficiency of folic acid promotes the activation of protooncogenes to oncogenes, which in consequence results in a decrease in the stability of cellular DNA. A study carried out by Giovannicci et al. showed that excessive alcohol consumption and folic acid deficiency associated with it increased the risk of developing colorectal cancer by almost four times. However, what cannot be overlooked, the results of clinical trials show us that very high doses and folic acid accumulation favor the development of some cancers. It is thought that excess of folic acid may lead to hypermethylation of DNA and, consequently, to inactivation of the suppressor genes responsible for controlling cell division. Women in the pre-contraceptive period, during pregnancy and breastfeeding are included in the group of people with a special need for folic acid, in whom deficiency can cause many negative effects. The presence of folic acid is necessary in the process of cell formation and growth in the developing fetus, especially when the neural tube is forming. Moreover adequate folic acid concentration decreases risk of fetal heart and urinary tract defects, and also reduces the occurrence of thrombosis and miscarriage in pregnant women. Steeweg-de Graaff J. et al. conducted evaluation of emotional and behavioral development at the age of 3 depending on the concentration of folates and homocysteine in the mother's blood plasma at an early stage of the pregnancy. It was noted that with insufficient folate supply, associated with a lack of or its late supplementation increases the risk of emotional problems in children. In addition, defects of the nervous system may occur as a result of dysfunction of folate metabolism. In its transformation pathway MTHFR reductase takes a particular role. Its reduced activity contributes to the impairment of folic acid metabolism, and the MTHFR gene - type 677CC is considered a risk factor for the development of neural tube defects. Randomized study compared pharmacokinetic parameters of [6S]-5-MTHF and folic acid in healthy women of childbearing age with different MTHFR genotypes (677TT n = 6, 677CC n = 8). Higher peak folate concentrations in plasma with [6S]-5-MTHF supplementation was found, in comparison with folic acid and not depending in the MTHFR genotype, as well as a shorter time needed to reach maximum concentration. In a different randomized, double-blind trial significantly higher folate levels in red blood cells were obtained in women receiving [6S]-5-MTHF. Studies confirm the hypothesis that nutritional deficiencies are of great importance in terms of fetal development. The results testify the need of folic acid supplementation, in which it is worth to consider the use of biologically active form, 12 weeks before planned pregnancy. In the second and third trimesters, the supplementation of folic acid is an important element in prevention of anemia caused by vitamin B12 and folic acid deficiency, i.e. megaloblastic anemia. Moreover, it was found that folic acid at a daily dose of 400 - 800 μg reduce the risk of fetal neural tube defects. In its guidelines, Polish Society of Gynecologists and Obstetricians (PTGiP) recommends supplementation of 400 μg / day of folic acid in women in low risk group in the pre-contraceptive period, pregnancy and during breastfeeding and supplementation of 800 μg/ day of folic acid in women in intermediate risk group and also high risk group in II and III trimester and during breastfeeding. It is worth emphasising that in most recent guidelines, PTGiP pays attention to the problem of folic acid metabolism and emphasizes the appropriateness of supplementation with its active form, especially at high doses. In folic acid metabolism, MTHFR catalyzes the synthesis to the active form of folate (L-5-MTHFR). It is necessary in the process of homocysteine degradation following remethylation to methionine. Unfortunately, as a result of inappropriate methylation, e.g. as a result of active form of folic acid deficiency, the concentration of homocysteine in the blood serum increases, which is responsible for various pathogenic processes in the body. Insufficient supply and improper metabolism of folic acid, as well as vitamins B6, B12 deficiency may be factors favorable for development of atherosclerosis and other diseases related to the cardiovascular system (e.g. heart attack, stroke, coronary artery disease). Excessively high concentration of homocysteine in the blood plasma, caused by disorders of its metabolic pathway in the body, is one of the reasons for the formation of atherosclerotic changes in blood vessels. Excess of homocysteine, with a simultaneous deficiency of folate and vitamin B12, damages the endothelium of blood vessels and increases oxidation processes, which are associated with the development of inflammation, oxidation of LDL cholesterol and change in the structure of the walls of blood vessels. In addition, the risk of developing peripheral thrombosis and hypertension increases. In the meta-analysis of Linda L. et al. it was found that high concentration of homocysteine is an independent factor of developing coronary heart disease. In the majority of studies, the risk of this disease is increased by 20% to 50% with every increase of concentration of homocysteine by 5 μmol /L in the blood of the examined persons. To ensure proper functioning of blood vessels and to reduce the risk of cardiovascular disease, one needs to provide adequate concentration of homocysteine in the body. Folates and their adequate supply with diet or supplementation play a key role in this process. Looking at the numerous clinical studies, available literature and the function of folic acid, it can be stated that it is an essential compound with multidirectional biological action, which is involved in the synthesis of amino acids and nucleic acids important for health. It plays an important role in tissues, such as: the fetus, hematopoietic system and gastrointestinal epithelium, in which cell divisions occur. For this reason, the presence of folic acid in the right amounts, ensures the proper functioning of our body. A deficiency of folic acid in the diet leads to a reduced concentration of folate in plasma and red blood cells. It is a condition that contributes to the formation of many serious diseases in our body and congenital neural tube defects in the fetus. As clinical studies have shown, the optimal concentration of folates in the blood reduces the risk of cardiovascular, circulatory, central nervous system diseases and certain types of cancer. To reduce the risk of diet-related diseases caused by folic acid deficiency, daily diet should be optimally balanced and contain products rich in natural folates. If diet is an insufficient source of folic acid, its supplementation should be considered, with the possible inclusion of its active form. Supplementation is recommended, in particular, for people with: megaloblastic anemia, diabetes mellitus, malabsorptions (e.g. Crohn's disease), alcoholism, malnutrition, neurodegenerative diseases (e.g. Alzheimer's disease), cardiovascular diseases, elevated homocysteine levels and using certain medications (e.g. oral contraceptives, metformin, methotrexate). It is also worth mentioning that metapholine supplementation bypasses the multistage metabolic process before incorporating folates into the cell cycle, as opposed to the inactive form of folic acid. This is particularly important for patients with the DHFR and MTHFR mutation, which depending on the polymorphism, may occur in up to 53% of the Caucasian population. Consequently, MTHFR reductase activity is reduced by up to 70%.Kwas foliowy jest niezbędny do właściwego funkcjonowania organizmu i zachowania homeostazy. Uczestniczy w metabolizmie kwasów nukleinowych, aminokwasów, syntezie pirymidyn i puryn. Syntetyczna postać kwasu foliowego nie wykazuje aktywności biologicznej. Przekształcana jest w szeregu reakcji do postaci folianów (L-5-MTHF) które, są transportowane do komórek, gdzie bierze udział w ważnych procesach biologicznych. Gen MTHFR odpowiedzialny jest za katalizę reakcji enzymatycznej: redukcję 5,10-metylenotetrahydrofolianu do aktywnej formy. Mutacja genu MTHFR 677C>T występuje nawet u 53% populacji czego konsekwencją jest zmniejszenie aktywności reduktazy – MTHFR nawet o 70%. Metafolina (aktywna forma) w przeciwieństwie do kwasu foliowego, aby zostać włączona do procesów metabolicznych w komórce, nie ulega redukcji, katalizowanej przez DHFR oraz MTHFR. Jest to istotne w szczególności dla osób, które mają mutację genu MTHFR oraz DHFR. Przyjmowanie niektórych leków osłabia wchłanialność kwasu foliowego. Kwas foliowy jest niezbędny do prawidłowego funkcjonowania organizmu człowieka a jego niedobór może indukować różne procesy chorobowe w organizmie, do których zaliczamy: powstawanie wad cewy nerwowej, zaburzenia w układzie nerwowym, niedokrwistość megaloblastyczną, negatywny wpływ na funkcjonowanie układu sercowo – naczyniowego oraz rozwój miażdżycy i nowotworów. Witamina ta bierze udział w powstawaniu ważnych neuroprzekaźników, takich jak: adrenalina, dopamina i noradrenalina, dlatego jej niedobór może prowadzić do powstania zaburzeń neuropsychiatrycznych. Niedobór kwasu foliowego sprzyja aktywacji protoonkogenów do onkogenów. Liczne badania kliniczne i dostępna literatura potwierdzają funkcję kwasu foliowego, że jest to niezbędny związek o wielokierunkowym działaniu biologicznym, który pełni istotną rolę w tkankach. Suplementacja metafoliną omija wieloetapowy proces metaboliczny w przeciwieństwie do nieaktywnej postaci kwasu foliowego

The effect of selenium, zinc and copper on the excretion of urinary modified nucleobases in rats treated with prostate cancer cells

Given the strong associations between diet and cancer risk, there is considerable scientific interest in determining whether dietary factors associated with prostate cancer cell implantation may influence epigenetic alternations. The aim of the research was to assess impact of selected trace elements (selenium, zinc and copper) on the kinetics of changes (10-13-14-21 week of life cycle of rats) in the level of 7-methylguanine, 3-methyladenine, 1-methylguanine and 8-oxo-guanine in the urine of rats with implanted prostate cancer cells (LNCaP). Modified nucleobases were determined by validated high performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) method using multiple reaction monitoring (MRM) mode. In the presented model the implantation of rats with cancer cells did not affect the level of the examined biomarkers in the rats’ urine. The level of methyl derivatives was statistically significantly reduced with the age of the examined rats. The implantation of rats with cancer cells results in the appearance of tumors in 71% of the rats obtaining the standard diet and respectively in 25% of those supplemented with selenium. Supplementation with selenium affects both the effectiveness of tumor induction and the concentration of 7-MeG, 3-MeA, 1-MeG and 8-oxoG in urine of the examined rats. These findings show that modified nucleosides can play an important role in cancer prevention

Title Changes in the Mineral Composition of Rat Femoral Bones Induced by Implantation of LNCaP Prostate Cancer Cells and Dietary Supplementation

Prostate cancer (PCa) is the second most frequent cancer in men and the fifth most common cause of death worldwide, with an estimated 378,553 deaths in 2020. Prostate cancer shows a strong tendency to form metastatic foci in the bones. A number of interactions between cancer cells attacking bones and cells of the bone matrix lead to destruction of the bone and growth of the tumour. The last few decades have seen increased interest in the precise role of minerals in human health and disease. Tumour cells accumulate various minerals that promote their intensive growth. Bone, as a storehouse of elements, can be a valuable source of them for the growing tumour. There are also reports suggesting that the presence of some tumours, e.g., of the breast, can adversely affect bone structure even in the absence of metastasis to this organ. This paper presents the effect of chronic dietary intake of calcium, iron and zinc, administered in doses corresponding maximally to twice their level in a standard diet, on homeostasis of selected elements (Ca, K, Zn, Fe, Cu, Sr, Ni, Co, Mn and Mo) in the femoral bones of healthy rats and rats with implanted cancer cells of the LNCaP line. The experiment was conducted over 90 days. After the adaptation period, the animals were randomly divided into four dietary groups: standard diet and supplementation with Zn, Fe and Ca. Every dietary group was divided into experimental group (with implanted cancer cells) and control group (without implanted cancer cells). The cancer cells (LnCaP) were implanted intraperitoneally in the amount 1 &times; 106 to the rats at day 90 of their lifetime. Bone tissue was dried and treated with microwave-assisted mineral digestation. Total elemental content was quantified by ICP-MS. Student&rsquo;s t-test and Anova or Kruskal&ndash;Wallis tests were applied in order to compare treatment and dietary groups. In the case of most of the diets, especially the standard diet, the femoral bones of rats with implanted LNCaP cells showed a clear downward trend in the content of the elements tested, which may be indicative of slow osteolysis taking place in the bone tissue. In the group of rats receiving the standard diet, there were significant reductions in the content of Mo (by 83%), Ca (25%), Co (22%), Mn (13%), K (13%) and Sr (9%) in the bone tissue of rats with implanted LNCaP cells in comparison with the control group receiving the same diet but without LNCaP implantation. Supplementation of the rat diet with calcium, zinc and iron decreased the frequency of these changes relative to the standard diet, which may indicate that the diet had an inhibitory effect on bone resorption in conditions of LNCaP implantation. The principal component analysis (PCA) score plot confirms the pronounced effect of implanted LNCaP cells and the standard diet on bone composition. At the same time, supplementation with calcium, zinc and iron seems to improve bone composition. The microelements that most often underwent quantitative changes in the experimental conditions were cobalt, manganese and molybdenum

The Effect of Genistein Supplementation on Cholesterol Oxidation Products and Fatty Acid Profiles in Serums of Rats with Breast Cancer

The aim of this study was to assess the effect of genistein on the level of cholesterol, oxysterols, and composition of fatty acids, as well as enzymatic activity of desaturases, in rats with breast cancer. The animals were supplemented with nano-, micro-, and macrogenistein. Rats were treated with 7,12-dimethylbenz[a]anthracene to induce mammary adenocarcinoma. In the case of animals supplemented with genistein, an increase in the intensity of the carcinogenesis process was observed. Genistein supplementation also affected the cholesterol and oxysterols levels, as well as the composition of fatty acids, in the serum of rats with neoplastic disease. Dietary supplementation with nanogenistein significantly increased the level of cholesterol (p = 0.02) and cholesterol oxidation products (p = 0.02), which may have significant impacts on cancer development and progression

The Influence of Supplementation with Zinc in Micro and Nano Forms on the Metabolism of Fatty Acids in Livers of Rats with Breast Cancer

The aim of this study was to investigate the effect of zinc supplementation (in the form of nano or microparticles) on the profile and metabolism of fatty acids in the liver microsomes of rats with induced breast cancer. The activity of desaturases (Δ5, Δ6, Δ9) and the level of cholesterol and its oxidized derivatives were measured. The aim of this study was also to determine the effect of various forms of zinc supplements on rats that were on 5-, 12- and 15-hydroxyeicosatetraenoic (5-, 12- and 15-HETE) and hydroxyoctadecadienoic (HODE) acids, and the level of prostaglandin E2 (PGE2). Female Spraque-Dawley rats (n = 24) were divided into 2 groups that were supplemented with zinc in the micro form (342 nm) or nano form (99 nm) particles, respectively, and a group with a standard diet (control group). All animals received 7,12-dimethylbenz[a]anthracene twice for the induction of breast cancer. Dietary nano-Zn supplementation increased vaccenic acid content (p = 0.032) and decreased Δ6-desaturase activity (p = 0.006), whereas micro-Zn increased cholesterol (p = 0.006), ∑COPs (total cholesterol-oxidation products) (p = 0.019) and PGE2 (p = 0.028) content. Dietary enrichment with Zn microparticles resulted in lower concentrations of the metabolites 15-, 12- and 5-HETE and HODE. Our study indicates that the effect of zinc supplementation on the metabolism of fatty acids in the liver microsomes under neoplastic conditions depends on the form in which it is administered