Combined supplementation of vanadium and fish oil suppresses tumor growth, cell proliferation and induces apoptosis in DMBA-induced rat mammary carcinogenesis

The anti-cancer activity of vanadium and fish oil has been shown in a large number of studies. This study was undertaken to analyze the combined effect of vanadium and fish oil on 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. The whole experiment was divided into three parts: (1) DNA strand breaks study, (2) morphological analysis, and (3) histological and immunohistochemical study. Rats were treated with DMBA (0.5 mg/0.2 ml corn oil/100 g body weight) by a tail vein injection. Rats received vanadium (w/v) as ammonium monovanadate at a concentration of 0.5 ppm (4.27 μmol/L) in the drinking water and given ad libitum and/or fish oil (0.5 ml/day/rat) by oral gavage. Histology, morphology, DNA strand breaks, cell proliferation, and apoptosis of the mammary tissue were assessed in this study. Treatment with vanadium or fish oil alone significantly reduced the DNA strand breaks, palpable mammary tumors, tumor multiplicity, and cell proliferation but the maximum protection effect was found in the group that received both vanadium and fish oil and the combination treatment offered an additive effect (P < 0.05). Furthermore, vanadium and fish oil significantly increased the TUNEL-positive apoptotic cells (P < 0.05) but the increase was maximal with combination treatment and had an additive effect. These results affirm the benefits of administration of vanadium and fish oil in the prevention of rat mammary carcinogenesis which was associated with reduced DNA strand breaks, palpable mammary tumors and cell proliferation and increased TUNEL-positive apoptotic cells.     

Protective role of fish oil (Maxepa) on early events of rat mammary carcinogenesis by modulation of DNA-protein crosslinks,cell proliferation and p53 expression

Background  

Fish oil is known to protect from many types of cancers of the colon, liver, breast, prostate and lung [1–3]. The objective of the present study was to evaluate the role of fish oil [Maxepa, supplemented at a dose of 0.5 ml is equivalent to 90 mg eicosapentaenoic acid (EPA) and 60 mg docosahexaenoic acid (DHA)] on cell proliferation, expression of p53 tumor suppressor protein and DNA protein crosslinks (DPCs) in a defined model of chemical rat mammary carcinogenesis. Mammary carcinogenesis was initiated by a single, intravenous (i.v.) tail vein injection of 7,12 dimethylbenz(α)anthracene (DMBA) at a dose of 5 mg DMBA/2 ml corn oil/kg body weight in female Sprague-Dawley rats at 7 weeks of age. Fish oil supplementation was started daily, 2 weeks prior to DMBA injection and continued for 24 (31 weeks of animal age) weeks and 35 (42 weeks of animal age) weeks of post DMBA injection, for histopathological and immunohistochemical and for morphological studies, respectively.     

Dietary intervention of cow ghee and soybean oil on expression of cell cycle and apoptosis related genes in normal and carcinogen treated rat mammary gland

The present study investigated the effect of cow ghee (clarified butter fat) versus soybean oil on the expression of cyclins A and D1, and apoptosis regulating Bax, Bcl-2 and PKC-α genes in mammary gland of normal and 7,12-dimethylbenz(a)anthracene (DMBA) treated rats. Two groups of 21 days old female rats were fed for 44 weeks diet containing cow ghee or soybean oil (10%). The animals were given DMBA (30 mg/kg body weight) through oral intubation after 5 weeks feeding. Another two groups fed similarly but not given DMBA served as respective controls. In control groups, the expression of cyclin A was similar on both cow ghee and soybean oil, but that of cyclin D1 was more on soybean oil diet. However, in DMBA treated groups, the expression levels of cyclins A and D1 were significantly greater on soybean oil than on cow ghee. The expression levels of Bax, Bcl-2 and PKC-α were similar in two control groups. However, in tumor tissue expression levels of Bcl-2 and PKC-α were significantly lower in cow ghee fed rats than in soybean oil fed ones, but Bax was similarly expressed in both DMBA treated groups. The pro-apoptotic ratio Bax/Bcl-2 increased and the anti-apoptotic ratio PKC-α*(Bcl-2/Bax) decreased in cow ghee group compared to soybean oil group in DMBA treated rats. Hence, the decreased expressions of cyclins A and D1, Bcl-2 and PKC-α mediate the mechanism by which cow ghee protects from mammary carcinogenesis.     

Protective role of vanadium on the early process of rat mammary carcinogenesis by influencing expression of metallothionein, GGT-positive foci and DNA fragmentation

Vanadium, a dietary micronutrient, is now proving to be a promising anti-tumour agent. The present study was conducted to ascertain its anti-neoplastic potential against an experimental mammary carcinogenesis. Female Sprague-Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(alpha)anthracene (DMBA; 0.5 mg per 100 g body weight) by a single tail vein injection in an oil emulsion. Vanadium (ammonium monovanadate) at a concentration of 0.5 p.p.m. was supplemented in the drinking water and given ad libitum to the experimental group immediately after the carcinogen treatment and it continued until the termination of the study (24 weeks for histological, immunological and biochemical observations and 35 weeks for morphological findings). It was found that vanadium treatment brought about substantial protection against DMBA-induced mammary carcinogenesis. This was evident from histological findings that showed substantial repair of hyperplastic lesions following supplementation of vanadium alone. There was a significant reduction in incidence (P<0.05), total number, multiplicity (P<0.01), size of palpable mammary tumours and delay in mean latency period of tumour appearance (P<0.001) following vanadium supplementation compared to the DMBA control. The immunohistochemical localization of metallothionein (a prognostic marker for breast cancer) showed reduced expression with vanadium treatment. Further, DNA fragmentation in the mammary tissue of the vanadium-treated group indicated apoptosis. In this group, vanadium also caused a significant decrease in the number (P<0.002) and focal area (P<0.05) of gamma-glutaminetranspeptidase-positive hepatic foci. The results clearly show the anti-neoplastic potential of vanadium.     

Therapeutic effect of paclitaxel and propolis on lipid peroxidation and antioxidant system in 7,12 dimethyl benz(a)anthracene-induced breast cancer in female Sprague Dawley rats

Breast cancer is one of the most common cancers in women of developed and developing countries. The optimum management of which requires a multidisciplinary approach including the use of certain biochemical and molecular markers. The effect of propolis along with paclitaxel on 7,12 dimethyl benz(a)anthracene (DMBA) induced experimental breast cancer was investigated in female Sprague Dawley rats. Female Sprague Dawley rats were divided into five groups of six animals each. Group I served as normal control animal. Group II animals received DMBA (20 mg in 0.5 ml sunflower oil and 0.5 ml of saline) i.p. to develop mammary tumor by the end of 90 days. Group III were breast cancer animals treated with 33 mg paclitaxel/kg body weight (bw) weekly once for 4 weeks. Group IV were breast cancer-bearing animals treated with 50 mg propolis/kg bw for 30 days. Group V were breast cancer-bearing animals treated with both paclitaxel and propolis as mentioned above. Administration of paclitaxel and propolis effectively suppressed breast cancer, which is revealed by the decrease in the extent of lipid peroxidation (LPO) with concomitant increase in the activities of enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) and non-enzymic antioxidants (reduced glutathione (GSH), Vitamin C and Vitamin E) levels when compared to breast cancer-bearing animals treated with either paclitaxel or propolis alone. From our results, we conclude that propolis is a potent antioxidant and, when given in combination with paclitaxel, offers maximum protection against DMBA induced mammary carcinogenesis.     

Apoptosis induction by S-allylcysteine,a garlic constituent,during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

The apoptosis-inducing capacity of S-allylcysteine (SAC), a water-soluble garlic constituent, during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch (HBP) carcinogenesis was investigated in male Syrian hamsters using DNA fragmentation and the apoptosis-associated proteins, tissue transglutaminase (tTG) and Bcl-2. Hamsters were divided into four groups of six animals each. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin on the right buccal pouches three times a week for 14 weeks. Group 2 animals painted with DMBA as in group 1, in addition received 200 mg kg(-1) body weight SAC orally on days alternate to DMBA application. Group 3 animals received SAC as in group 2. Group 4 animals received neither DMBA nor SAC and served as the control. The experiment was terminated at the end of 14 weeks. Administration of SAC (200 mg kg(-1) body weight) to animals painted with DMBA inhibited DMBA-induced HBP carcinogenesis as revealed by the absence of neoplasms, induction of tTG and inhibition of Bcl-2 expression. The results of the present study suggest that SAC may exert its chemopreventive effect by inducing apoptosis.     

Combinatorial effect of fish oil (Maxepa) and 1α,25-dihydroxyvitamin D3 in the chemoprevention of DMBA-induced mammary carcinogenesis in rats

The present study demonstrates the anti-tumor effects of combined supplementations of dietary fish oil (Maxepa) and 1α,25-dihydroxyvitamin D₃ (vitamin D₃) on 7,12-dimethylbenz(α)anthracene (DMBA)-induced rat mammary carcinogenesis. Female Sprague–Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(α)anthracene (DMBA; 0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion. Both fish oil (rich in EPA and DHA) and vitamin D₃ were administered orally at a dose of 0.5 ml/day/rat and 0.3 μg/100 μL propylene glycol twice a week respectively and continued to 35 weeks after DMBA administration. Fish oil in combination with vitamin D₃ resulted in a significant reduction in incidence, multiplicity and volume of mammary tumors. These supplementation also inhibited DMBA-induced mammary 7-methylguanine DNA adducts formation, which was measured by HPLC-fluorescence assay (at four sequential time points; ANOVA, F = 42.56, P < 0.0001). Immunohistochemical analysis revealed that the effect of fish oil and vitamin D₃ occurred through suppression of cell proliferation (BrdU-LI: P < 0.0001). Fish oil and vitamin D₃ together also reduced the mRNA expression of iNOS (84%, P < 0.05). In view of their natural availability, non-toxicity and acceptability; combined supplementation of fish oil and vitamin D₃ might be effective for chemoprevention of mammary carcinogenesis.     

IL-10 基因对糖尿病大鼠胰岛beta细胞凋亡的保护作用

目的：研究白细胞介素10（IL-10）基因对链脲佐菌素(STZ)诱导的糖尿病大鼠胰腺炎症浸润程度及胰腺组织中Bcl-2 及Bax 表达的影响。方法：建立链脲佐菌素性糖尿病模型,腺病毒介导的IL-10 基因(Ad-mIL-10)腹腔注射。检测大鼠空腹血糖值;免疫组 织化学法观察胰腺炎症浸润程度;TUNEL法检测胰岛细胞凋亡;免疫组化方法观察Ad-mIL-10 对实验性糖尿病大鼠胰岛凋亡调 控基因Bax 和Bcl-2 表达的影响。结果：Ad-mIL-10 腹腔注射糖尿病发病率低,平均血糖水平低,可以降低胰腺炎症浸润程度,减 少胰岛细胞凋亡。给予Ad-mIL-10 后大鼠Bax 基因的表达明显下降, Bcl-2 与Bax 的比值明显增加。结论：IL-10基因对实验性糖 尿病大鼠有降血糖作用,减少胰岛细胞凋亡,与调节Bcl-2 与Bax 基因的表达有关。     

Antiproliferative and apoptosis inducing effect of lactoferrin and black tea polyphenol combination on hamster buccal pouch carcinogenesis

Combination chemoprevention using tea polyphenols as one of the components has received growing consideration in recent years. The present study was designed to evaluate the antiproliferative and apoptosis inducing effects of bovine lactoferrin (bLF) and black tea polyphenol (Polyphenon-B: P-B) combination on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Topical application of DMBA for 14 weeks induced buccal pouch tumours that showed aberrant expression of cytokeratins, a marker for epithelial carcinomas. This was associated with increased cell proliferation and evasion of apoptosis as revealed by upregulation of proliferating cell nuclear antigen, NF-kappaB, mutant p53, Bcl-2 and downregulation of Bax, Fas and caspase 3 protein expression. Although dietary administration of bLF and Polyphenon-B alone significantly reduced tumour incidence, combined administration of bLF and Polyphenon-B was more effective in inhibiting HBP carcinogenesis by restoring normal cytokeratin expression, inhibiting cell proliferation and inducing apoptosis. These findings suggest that a "designer item" approach will be useful for human oral cancer prevention strategies.     

Suppression of cell proliferation, DNA protein cross-links, and induction of apoptosis by vanadium in chemical rat mammary carcinogenesis

Vanadium, a dietary micronutrient, has recently been considered as an important pharmacological agent. The present investigation was carried out to ascertain its anticarcinogenic potential against an experimental rat mammary carcinogenesis. Female Sprague-Dawley rats were treated with 7,12dimethylbenz(alpha)anthracene (DMBA) (0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion. Vanadium (ammonium monovanadate) at a concentration of 0.5 ppm (4.27 micromol/L) was supplemented in drinking water and given ad libitum to the experimental group. The present study was an attempt to assess the effect of vanadium (ammonium monovanadate) on cell proliferation, apoptosis and histopathology in the mammary tissue. We also have examined DNA fragmentation and DNA protein cross-links (DPC) in the liver of rats as well. Immunohistochemical analysis indicated that early neoplasia in mammary tissue proceeds by a decrease in apoptotic cell death (ACD), which was also examined with TUNEL assay, rather than an increase in cell proliferation (P<0.01). DPC in liver were reduced by vanadium treatment (ANOVA, F=13.7, P<0.01). Agarose gel electrophoresis revealed DNA fragmentation in the vanadium-treated group, confirming apoptosis further. Results of the study indicate that the mammary preneoplasia is sensitive to vanadium intervention whereas normal proliferating cells are not.     

Zingerone induced caspase‐dependent apoptosis in MCF‐7 cells and prevents 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinogenesis in experimental rats

Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12‐dimethylbenz(a)anthracene (DMBA)‐treated mammary carcinogenesis in Sprague‐Dawley (SD) rats and MCF‐7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA‐induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt‐b₅ and CYP₄₅₀) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl‐2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA‐induced mammary cancer in SD animals and Michigan cancer foundation‐7 mammary cancer cells.     

IL-10基因对糖尿病大鼠胰岛β细胞凋亡的保护作用

目的：研究白细胞介素10（IL-10）基因对链脲佐菌素（STZ）诱导的糖尿病大鼠胰腺炎症浸润程度及胰腺组织中Bcl-2及Bax表达的影响。方法：建立链脲佐茵素性糖尿病模型,腺病毒介导的IL-10基因（Ad-mIL-10）腹腔注射。检测大鼠空腹血糖值;免疫组织化学法观察胰腺炎症浸润程度;TUNEL法检测胰岛细胞凋亡;免疫组化方法观察Ad-mIL-10对实验性糖尿病大鼠胰岛凋亡调控基因Bax和Bcl．2表达的影响。结果：Ad-mlL-10腹腔注射糖尿病发病率低,平均血糖水平低,可以降低胰腺炎症浸润程度,减少胰岛细胞凋亡。给予Ad-mlL-10后大鼠Bax基因的表达明显下降,Bcl-2与Bax的比值明显增加。结论：IL-10基因对实验性糖尿病大鼠有降血糖作用,减少胰岛细胞凋亡,与调节Bcl-2与Bax基因的表达有关。     

Expression of apoptosis-related proteins in involuting mammary gland of sow

The expression of apoptosis-related proteins: TGF-β1 (local inductor), TGF-β-receptor, Bax (promoter), Bcl-2 (inhibitor) and CPP-32 (executor of apoptosis); the subcellular distribution of Bax; as well as the number and morphology of apoptotic cells in low-, moderate-, and high-involuted mammary glands of sow (four to six days after weaning) were investigated. The immunohistochemical study demonstrated a statistically significant increase in the integrated optical density (IOD) of lobuloalveolar mammary tissue labelling with anti-Bax antibody from low- through moderate-, to high-involuted glands. The immunoelectron microscopy revealed that Bax was localised in the cytosol, on the membranes of mitochondrium and rough endoplasmic reticulum, in nuclear envelope pores, and over heterochromatin of mammary epithelial cells. The increase in Bax/Bcl-2 ratio (2.3, 2.6 and 5.6 for low-, moderate-, and high-involuted glands, respectively) indicated the increasing susceptibility of mammary epithelial cells to apoptosis in the course of involution. The highest Bax/Bcl-2 ratio in high-involuted glands coincided with the highest expression of CPP-32 (caspase 3), TGF-β1 and TGF-β1 receptor. The number of apoptotic cells (simultaneous TUNEL and Hoechst 33342 staining) was 2.7, 3.4 and 3.8% for low-, moderate-, and high-involuted glands, respectively. The ultrastructural evaluation showed characteristic morphological features of apoptosis such as: margination and condensation of chromatin; pyknosis and fragmentation of the nucleus; and formation of apoptotic bodies. Phagocytosis of apoptotic cells by macrophages was also documented. The results of the present study suggest the involvement of Bax/Bcl-2 check-point in the regulation, CPP-32 in the execution, but TGF-β1 in the induction of apoptosis of mammary epithelial cells in the involuting mammary gland of sow.     

姜黄素对过度训练大鼠肾脏细胞凋亡的调控作用及其机制

目的：探讨姜黄素对过度训练所致大鼠氧化应激、肾脏细胞凋亡的作用及其机制。方法：7周龄SPF级雄性Wistar大鼠分为对照组（C组,n=12）、过度训练组（OM组,n=11）、姜黄素+过度训练组（COM组,n=14）。C组不进行任何运动干预,OM组、COM组大鼠进行8周递增负荷游泳训练。训练期间,COM组以200 mg/（kg·d）、5 ml/kg姜黄素进行灌胃,其他组灌胃等体积0.5%浓度羧甲基纤维素纳。末次训练后24 h,光镜观察肾脏组织病理学改变,取血液、肾脏组织检测相关生化指标。结果：8周递增负荷游泳训练后,光镜下C组大鼠肾脏组织结构正常;OM组出现组织病理学改变;COM组较OM组减轻。与C组比较,OM组血清皮质酮（Cor）、肌酐（Cr）和尿素氮（BUN）水平均升高（P<0.01）,睾酮（T）水平降低（P<0.01）;肾脏核因子E2相关因子2（Nrf2）表达水平无显著变化（P>0.05）,血红素氧合酶1（HO-1）表达水平降低（P<0.05）,总抗氧化能力（T-AOC）和超氧化物歧化酶（SOD）活性降低（P<0.01）,丙二醛（MDA）浓度升高（P<0.01）;肾脏细胞凋亡水平升高（P<0.01）,肾脏抗凋亡蛋白B淋巴细胞瘤因子-2（Bcl-2）表达减弱（P<0.01）,促凋亡蛋白Bcl-2相关X蛋白（Bax）表达增强（P<0.01）。与OM组比较,COM组血清Cor水平（P<0.01）降低,T水平升高（P<0.01）,Cr和BUN水平均降低（P<0.05）;肾脏Nrf2和HO-1表达增强（P<0.05）,T-AOC和SOD活性升高（P<0.01）,MDA浓度降低（P<0.05）;肾脏细胞凋亡水平降低（P<0.05）,Bcl-2表达增强（P<0.05）,Bax表达减弱（P<0.01）。组间T/Cor比值变化趋势与T变化相一致,Bcl-2/Bax比值变化趋势与Bcl-2变化相一致。结论：8周递增负荷游泳训练引发大鼠过度训练,氧化应激加剧并加速肾脏细胞凋亡,肾脏组织发生病理改变及功能异常。姜黄素通过上调Nrf2、HO-1蛋白表达,有效缓解过度训练引发的氧化应激,从而增强Bcl-2表达,减弱Bax表达,抑制大鼠肾脏细胞凋亡,保护肾脏组织结构和功能正常。     

姜黄素对过度训练致大鼠脾脏细胞凋亡的调控作用及其机制*

目的:研究姜黄素调控Keap1-Nrf2-ARE信号通路缓解大鼠过度训练所致脾脏氧化应激及细胞凋亡机制。方法:7周龄SPF级雄性Wistar大鼠分为对照组(C组,n=12)、过度训练组(OM组,n=11)、姜黄素+过度训练组(COM组,n=14)。C组不进行任何运动干预,OM组、COM组大鼠进行8周递增负荷游泳训练。训练期间,COM组以200 mg/(kg·d)、5 ml/kg姜黄素进行灌胃,其他组灌胃等体积0.5 %羧甲基纤维素纳助溶剂。末次训练后24 h,称重计算脾脏指数,光镜观察脾脏组织病理学改变,取血液、脾脏组织检测相关生化指标。结果:C组大鼠脾脏组织结构正常;OM组较C组脾脏指数极显著降低(P＜0.01),并出现明显病理学改变;COM组较OM组脾脏指数显著升高(P＜0.05),且组织形态学改变有所改善。与C组比较,OM组血清皮质酮(Cor)浓度和脾脏细胞凋亡水平、丙二醛(MDA)浓度均升高,促凋亡蛋白Bcl-2相关X蛋白(Bax)表达增强(P＜0.05或P＜0.01);体重、血清睾酮(T)水平及脾脏超氧化物歧化酶(SOD)活性降低,脾脏血红素氧合酶1(HO-1)、抗凋亡蛋白B淋巴细胞瘤因子-2(Bcl-2)表达减弱(P＜0.05或P＜0.01);脾脏核因子E2相关因子2(Nrf2)表达水平无显著变化(P＞0.05)。与OM组比较,COM组体重无显著变化(P＞0.05);血清T浓度升高,脾脏SOD活性升高,Bcl-2、Nrf2和HO-1表达增强(P＜0.05或P＜0.01);血清Cor浓度及脾脏MDA浓度、细胞凋亡水平、Bax表达均降低或减弱(P＜0.05或P＜0.01);组间T/Cor比值变化趋势与T变化相一致,Bcl-2/Bax比值变化趋势与Bcl-2变化相一致。结论:8周递增负荷过度游泳训练引发脾脏细胞凋亡加剧,脾脏组织发生病理改变及功能异常。姜黄素通过上调Nrf2、HO-1蛋白表达,在一定程度上缓解过度训练引发的氧化应激,增强抑凋亡蛋白Bcl-2表达,减弱促凋亡蛋白Bax表达,改善大鼠脾脏细胞过度凋亡,保护脾脏组织结构和功能正常。     

Intestinal absorption of fish oil in rats previously adapted to diets containing fish oil or corn oil.

A study was conducted to evaluate whether the composition of previous dietary fat affects the absorption and composition of lymph obtained after a meal of fish oil. Adult male Sprague-Dawley rats were fed diets containing either corn oil or fish oil (MaxEPA) for 2 weeks. They were then given intraduodenally a bolus of an emulsion of 0.5 ml of fish oil plus 0.5 ml of 20 mM sodium taurocholate. Intestinal lymph was collected from a cannula in the main intestinal lymph trunk for various times after oil administration. Rats proportion of the test dose fo fish oil than those fed corn oil. There was an effect of previous diet on the fatty acid composition of the lymph. Rats fed fish oil had a higher percentage of eicosapentaenoic and docosahexaenoic acids in the lymph lipids than those fed corn oil while those fed corn oil had a higher percentage of linoleic acid. These results rule out decreased intestinal absorption as a mechanism for the hypotriacylglycerolemic effect of dietary fish oils. They also indicate a significant contribution of endogenous lipids to the fatty acids in lymph.     

Paeonol exhibits anti-tumor effects by apoptotic and anti-inflammatory activities in 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis

We investigated the preventive potential of paeonol on 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. Oral tumors were developed in the buccal pouches of Syrian golden hamsters using topical application of 0.5% DMBA three times/week for 10 weeks. DMBA treated hamsters developed hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. The animals also exhibited increased lipid oxidation, decreased antioxidant status and altered levels of detoxification agents. Paeonol treatment of DMBA treated hamsters for 14 weeks decreased tumor incidence, volume and burden Paeonol treatment also increased antioxidant activity and decreased lipid oxidation to near normal levels. Histomorphology and the expression patterns of mutant p53, cyclo-oxygenase (COX-2) and caspase-9 were investigated in the oral buccal mucosa. Paeonol exhibited protective effects against DMBA induced oral carcinogenesis owing to its antitumor, antioxidant, anti-inflammatory and apoptosis inducing properties.     

Dietary lipids differentially modulate the initiation of experimental breast carcinogenesis through their influence on hepatic xenobiotic metabolism and DNA damage in the mammary gland

Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA administration and raised the activity of CYP1s in the hours immediately after induction, while reducing the activity of Phase II enzymes, mainly NQO1. The levels of reactive metabolites measured in plasma by GC–MS and DMBA-DNA adducts in the mammary gland of the animals fed the high corn oil diet were also higher than in the other groups. On the other hand, the high extra-virgin olive oil diet and the control low-fat diet exhibited better coordinated Phase I and Phase II activity, with a lower production of reactive metabolites and less DNA damage in the mammary gland. The concordance between these effects and the different efficacy of the carcinogenesis process due to the dietary treatment suggest that lipids may differently modify mammary gland susceptibility or resistance to cancer initiation over the exposure to environmental carcinogens.SummaryDietary lipids influence the initiation of DMBA-induced mammary cancer through the modulation of liver xenobiotic metabolism, formation of reactive metabolites and subsequent DNA damage in the target tissue.     

Medium-term tongue carcinogenesis assays: A comparative study between 4-nitroquinoline 1-oxide (4NQO)-induced rat and dimethylbenzanthracene (DMBA)-induced hamster carcinogenesis

The most used animal models in oral cancer research are the hamster treated by dimethylbenzanthracene (DMBA), and the rat treated by 4-nitroquinoline 1-oxide (4NQO). The purpose of this study was to compare the DMBA-induced hamster tongue carcinogenesis and 4NQO-induced rat tongue carcinogenesis by means of morphological analysis. Male Wistar rats were distributed into three groups of ten animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. A total of 18 Syrian golden hamsters were submitted to 0.5% DMBA (dissolved in acetone) topical application three times/week for 4, 12 and 20 weeks. The primary histopathological change i.e., hyperplasia and hyperkeratosis, was evidenced after 4 weeks treatment with DMBA. Regarding 12 weeks treatment, 4NQO and DMBA were able to induce morphological changes as depicted by hyperplasia and dysplasia. At 20 weeks, squamous cell carcinoma was found in the majority of animals for both carcinogens used. Taken together, our results suggest that the hamster experimental model disclosed aspects related with tongue carcinogenesis in lesser time than rats. Probably, such discrepancies depend strongly on route of administration and the susceptibility with respect to animal species.