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Abstract: We investigated the effects of certain dietary polyunsaturated fatty acids (PUFAs) and related eicosanoids on the growth and metastasis formation of a murine mammary gland adenocarcinoma. Salvia hispanica (ChO) and Carthamus tinctorius (SaO) vegetable oil sources of ω-3 and -6 PUFAs and a commercial diet as control (CO), were used. We analysed fatty acids of neoplastic cells (NC) membranes by GLC; the eicosanoids 12- HETE and 12-HHT (LOX and COX metabolites) by HPLC and apoptosis and T-lymphocyte infiltration by flow cytometry and microscopy. NC from ChO groups showed lower levels of arachidonic acid and of both eicosanoids compared to SaO and CO (p<0.05). The ChO diet decreased the tumor weight and metastasis number (p<0.05). Apoptosis and T-lymphocyte infiltration were higher and mitosis decreased with respect to the other diets (p<0.05). Present data showed that ChO, an ancient and almost unknown source of ω-3, inhibits growth and metastasis in this tumor model. [Copyright &y& Elsevier]

Abstract: We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3–10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively. Conclusion: Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process. [Copyright &y& Elsevier]

Abstract: The purpose of this work was to analyze the effect of diets that contain several oils whose composition in fatty acids were different, on the kinetic parameters of the gamma-glutamyltranspeptidase (GGTP) and the lipoperoxidation of the epididymis because GGTP controls the level of the glutathione that is an molecule that regulates the level of oxidation protecting the maturation and survival of sperm in the lumen of the epididymis. The caput portion of the epididymis was chosen because the epithelium of this segment synthesizes GGTP. Weaned BALB-c mice were fed a commercial or semi-synthetic diet that contained 5% added olein. The mice were maintained on corn oil or fish oil diet for the first 4–8 months of age. The kinetic variables of the GGTP enzyme, analyzed by means of multiple regression analysis using dummy variables, showed that values were similar in olein and corn oil samples, whereas in samples from the fish oil fed group the enzyme behaved as that in animals maintained on commercial diets. Although there were no variations in maximum velocity (V m) of the enzyme, the K m value, was greater (P <0.0001) for the mice fed the olein and corn diets. These groups contained greater percentages of the monounsaturated fatty acids, palmitoleic (16:1 n-7) and oleic acid, 18:1 n-9. Similarly, the amount of lipid peroxidation was also greater in the olein and corn oil groups with respect to commercial and fish groups. The significant increment in K m of GGTP in the olein and corn groups was correlated with greater amount of monounsaturated fatty acids and lipid peroxidation in the epididymis. In conclusion, modifications of dietary lipid sources differentially modulated the epididymis tissue fatty acid profile, lipid peroxidation amounts, and the K m of GGTP. These effects may alter the metabolism of the natural substrate of GGTP, glutathione, a tripeptide with a powerful antioxidant activity, which is necessary in maintaining the oxidative state of the sperm microenvironment, thereby favoring maturation of the male gametes. [Copyright &y& Elsevier]

Abstract: Dietary arachidonic acid (AA) and eicosanoids influence neoplastic cell (NC) growth, differentiation and apoptosis. Plasma membrane fatty acid and cyclooxygenase (COX) and lipoxygenase (LOX) products were investigated in lung alveolar carcinoma cells from mice fed on different diets. Two groups were fed on a basic diet plus 6% of: corn oil (rich in 18:2n-6; CO) and on olein oil (rich in 18:1n-9; O), respectively. Control group (C) received commercial diet. NC fatty acids were analyzed by GLC, and apoptosis by flow cytometry and microscopy. In NC from CO group AA levels and LOX metabolites were increased, whereas COX metabolites decreased. NC from CO compared to O group diet showed a higher count of apoptosis and increased LOX:COX ratio. High levels of AA and decreased COX eicosanoids has been involved in anti-tumoral mechanisms by increasing tumor cell apoptosis. Present data emphasizes the implications of the dietary fatty acids on the neoplastic process in this tumoral model. [Copyright &y& Elsevier]

The essential fatty acid deficiency (EFAD) is a metabolic condition related to cancer development. We studied the effect of eicosapentaenoic acid (EPA, 20:5 n-3) and eicosatrienoic acid (ETA, 20:3 n-9), an essential fatty acid (EFA) and non-EFA respectively, on tumour cells parameters linked to tumour progression and metastases. Human tumour cell lines (T-24 from urothelium, MCF-7 from breast and HRT-18 from colon) were used. EPA showed an anti-proliferative effect on the three lines. ETA showed the following effects: in T-24, the lipid peroxidation was decreased and E-cadherin was undetectable; in MCF-7, increased E-cadherin expression enhanced the lipid peroxidation and decreased cell proliferation; on HRT-18, the E-cadherin expression and lipid peroxidation diminished, whereas cell proliferation was increased. In conclusion, EFA (20:5 n-3) exhibited beneficial effects, whereas unusual ETA showed an opposite effect on some tumour parameters. The possible riskiness of EFA-deprivation, along with the potential of EFA as natural nutrapeutic products for human tumour prevention and treatment, makes EFA worthy of further consideration. [Copyright &y& Elsevier]

Abstract: Chronic toxic effects of arsenic resulting from drinking water are a human health problem, especially in South-America and Asia. Arsenic is capable of influencing various cellular processes, causing adverse effects, including cancer. Although the exact mechanism of the action is not known, a correlation between oxidative stress, tumour promotion and arsenic exposure has been observed. We examined the effects of silymarin and quercetin, in counteracting oxidative stress produced by acute or sub-chronic sodium arsenite exposure. The stress responses to arsenite included an increase in the heat shock protein 70kDa expression, lipid peroxidation assayed by conjugated dienes measure, and γ-glutamyl-transpeptidase activity. We found that all these stress responses were eliminated by silymarin and quercetin in acute experiments. Both flavonoids diminished the conjugated dienes formation during sub-chronic cultures. Our results suggest that these antioxidant flavonoids, which may be easily incorporated into the diet, may afford a protective effect against arsenite-induced cytotoxicity. [Copyright &y& Elsevier]

Cell proliferation and apoptosis as well as cell–cell adhesion and communication are essential processes that assure cell survival, renewal and coordination. Since junctional proteins have a tumor suppressor activity, their immunohistochemical characterization has diagnostic and prognostic value. The purpose of this report is to review the role played by junctional and proliferation-related proteins in the salivary glands and to illustrate their immunohistochemical localisation in normal murine submandibular gland. Normal salivary gland tissue was obtained from normal adult male BALB/c mice. After immediate fixation in formalin and ethanol, the samples were immunohistochemically stained for E-cadherin (HECD-1), Bcl-2, Ki67 (MIB-1), connexin26 and connexin 32, β-catenin and γ-catenin. Their topological distribution and reactivity were evaluated by light microscopy. The nuclei of submandibular acinar cells exhibited low to moderate staining for Ki67, but no reaction was observed in ductal cells. Murine Bcl-2 was light to moderately expressed in the latero-basal domain of cells of submandibular acini but was only lightly expressed in striated and eosinophilic ducts. The lateral domain of acinar cells were heavily stained with anti-E-cadherin, while only low levels were expressed at the cellular surface of ducts. β-Catenin was consistently and evenly distributed along the latero-apical boundaries of eosinophilic secretory duct cells as well as on the lateral domain of acinar cells. On the contrary, γ-catenin was generally expressed at lower levels than β-catenin, was not expressed in ductal cells and was only lightly stained on the lateral membranes of acinar cells. No expression of connexin 32 was observed in ducts but it was significantly expressed in a spotted pattern along the plasma membrane of acinic cells. Connexin 26 showed similar localization to that of connexin 32 but the staining was much more intense. Since these proteins have been reported to play key roles in maintaining homeostasis via control of cell growth, differentiation and death, their analysis in normal salivary tissue will hopefully contribute to the study of salivary tumorigenesis. [ABSTRACT FROM AUTHOR]

The modulatory effects of polyunsaturated fatty acids (PUFA) on urinary tract tumorigenesis of 275 Wistar rats were evaluated by treating animals with the tumorigenic agent melamine. Rats were fed with formulae containing 6% of 4 varieties of fats: fish oil enriched in n-3 PUFA (FO), corn oil enriched in n-6 (CO), olein containing mainly n-9 oleic acid (O), and 98% stearic acid (SA), the latter two being essential (EFA)-deficient inducers. Two commercially fed control groups with (CM) and without (C) melamine were used. Animals were autopsied at 22–25 and at 36–40weeks. Hepatic fatty acids showed that O and SA groups were EFA-deficient. Simple well differentiated hyperplasias were significantly higher in the FO lot, whereas dysplasia was increased in the CO, O and SA lots. Most of the animals fed for 36–40weeks with the three latter formulae developed the more severe lesions. Increased urothelial proliferation was more frequent in EFA-deficient rats. The apoptosis/mitosis ratio was higher in O, SA and CO fed animals with respect to FO and chow ones. Results show that dietary PUFA modulate differentially both normal and pre-neoplastic urothelial proliferation induced by melamine. FO, rich in n-3 fatty acids, showed a strong protective effect. [Copyright &y& Elsevier]