pH-responsive PEG-chitosan/iron oxide hybrid nanoassemblies for low-power assisted PDT/PTT combination therapy.

Aim: To develop a hybrid nanoassembly platform using PEG-chitosan/iron oxide nanoparticles for effective low-power assisted photodynamic/photothermal combination therapy. Materials & methods: The hybrid nanoassemblies (NAs) were firstly fabricated by self-assembling chitosan and iron oxide nanoparticles, following which their surfaces were modified with polyethylene glycolated triphenylphosphine and loaded with methylene blue (MB) photosensitizer. The physical characteristics and phototherapy effects of these NAs were evaluated. Results: The formed MB-loaded NAs could produce both heat and singlet oxygen under low-power near-infrared irradiation, which would damage the cancer cells. Delivered by intravenous injection, the MB-loaded NAs showed high tendency to accumulate at the tumor sites, which would lead to effective cancer treatment under controlled photoexcitation without damaging the normal tissues. Conclusion: The proposed low-power assisted simultaneous photodynamic/photothermal approach effectively improves treatment efficiency and provides safe and precise treatment option.

Evaluation of behavioral profiles in mice fed with milk supplemented diets derived from human lactoferrin gene-modified cows.

To date, many safety assessments of genetically modified (GM) food have been done, but there was still considerable skepticism about the safety of genetic modified foods because no study could be designed to discover all of the potential effects. Since behavioral endpoints could provide one of the most sensitive strategies to reveal subtle functional deficits. In the present study, behavioral profiles in mice fed with milk derived from human lactoferrin gene-modified cows were investigated to enrich the toxicological data of GM food. Conventional milk and GM milk were added to diets at a proportion of 7.5%, 15% and 30%(w/w). After the mice consuming different diets for 30 days, a battery of behavioral tests were conducted to evaluate motor, sensory and cognitive functions. No significant differences were observed in spontaneous activity, grip strength and nociception between the treatment groups. And animals of different groups exhibited similar performance in rotarod, dark box, step-down and MORRIS water maze task. The study suggested that mice fed with conventional milk or human lactoferrin gene-modified milk had similar motor, sensory and cognitive functions.

Tocopherols inhibit esophageal carcinogenesis through attenuating NF-κB activation and CXCR3-mediated inflammation.

Esophageal cancer is one of the common causes of cancer mortality in the world. The predominant histological subtype, esophageal squamous cell carcinoma (ESCC), often results in poor prognosis due to the lack of effective approaches for the early diagnosis and treatment, highlighting the need for preventive intervention against this disease. Here we report that dietary tocopherols significantly prevents esophageal carcinogenesis by inhibiting the activation of NF-κB and the subsequent interaction of chemokine CXCL9/10/11 with their receptor CXCR3 in ESCC induced by N-nitrosomethylbenzylamine (NMBA) in murine models. Dietary supplementation with 0.15% α-tocopherol (α-T), δ-tocopherol (δ-T), or γ-tocopherol rich mixture (γ-TmT) markedly suppressed the production of pro-inflammatory cytokines, as well as the induction of CXCR3+ effector T cells (CD4+ Th1 and CD8+ CTLs) infiltration, especially at the early stage of carcinogenesis. In experiments in vivo and in vitro, these events were tightly correlated with the blockade of NF-κB activation. Our results show that tocopherols decrease carcinogenesis through inhibiting NF-κB and CXCR3 signaling, as well as related inflammation in early premalignant lesions. This pathway may offer a novel target for chemoprevention of esophageal cancer.

Alpha-Tocopherol prevents esophageal squamous cell carcinoma by modulating PPARγ-Akt signaling pathway at the early stage of carcinogenesis.

The poor prognosis of esophageal squamous cell carcinoma (ESCC) emphasizes the urgent need to better understand the carcinogenesis and develop prevention strategies. Previous studies have highlighted the potential of using Vitamin E (tocopherols) for cancer chemoprevention, but the preventive activity of α-Tocopherol against ESCC remains to be elucidated. Our data showed that early-stage supplementation with α-Tocopherol significantly prevented esophageal carcinogenesis induced by N-nitrosomethylbenzylamine (NMBA) in ESCC rat model. In the Het-1A cell model, α-Tocopherol markedly suppressed cell proliferation, promoted cell cycle G2-phase arrest and increased apoptosis. Gene microarray and proteins array analysis indicated that Akt signaling was a potential target for α-Tocopherol. We further demonstrated that α-Tocopherol increased the expression of PPARγ and its downstream tumor suppressor PTEN. Knockdown of PPARγ activated Akt signaling transduction, whereas this process was attenuated by the presence of α-Tocopherol and PPARγ agonist Rosiglitazone. In contrast, the effect of α-Tocopherol on Akt inhibition was not observed in established tumors, neither in cancerous cell lines which constitutively expressed higher levels of PPARγ. These results were closely correlated with the ineffectiveness of α-Tocopherol in the late stage of ESCC carcinogenesis. Taken together, our study suggested that α-Tocopherol may serve as a PPARγ agonist for the chemoprevention of esophageal cancer.

Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.

Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner.

Broccoli seed extract: Genotoxicity and subchronic toxicity studies.

Potential health benefits have been attributed to broccoli consumption. Hence, there is potential for use of broccoli seed extract (BSE) in food or for use as a dietary supplement. To assess the potential safety of a BSE product, three genotoxicity experiments, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality assay, were carried out. BSE was subject to an acute oral toxicity test and was evaluated in a 30-day feeding study in rats. BSE showed no mutagenic activity in the Ames assay and no evidence of genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). The LD50 of BSE in rats was >10 g/kg bw/d. In the 30-day feeding study, in which BSE was administered in the diet to provide doses of 0, 0.3, 1.0, or 3.0 g/kg bw/d, no toxicological significant effects were noted on body weight, body weight gain, organ weights, or on the results of hematological, clinical chemistry and histopathological evaluations. The no-observed-adverse-effect level was considered to be 3.0 g/kg bw/d, the highest dose tested. Collectively, these results support the safe use of BSE as a food ingredient or product.

[Food allergy:definitions, prevalence, diagnosis and therapy].

Food allergy is phenotypically an extremely heterogeneous group of diseases affecting multiple organs, sometimes in an isolated way, sometimes simultaneously, with the severity of reactions ranging from mild and local to full-blown anaphylaxis. Mechanistically, it is defined as a Th2-driven immune disorder in which food-specific IgE antibodies are at the basis of immediate-type adverse reactions. The sites of sensitization and symptoms do not necessarily overlap. Food allergy, which is the theme of this paper, is often confused with other adverse reactions to food of both animmune (e.g., celiac disease) and non-immune (e.g., lactose intolerance) nature. To reliably diagnose food allergy, a careful history (immediate-type reactions) needs to be complemented with demonstration of specific IgE (immune mechanism) and confirmed by an oral challenge. Co-factors such as exercise, medication, and alcohol may help trigger food allergy and further complicate accurate diagnosis. Where food extract-based diagnostic tests are poorly correlated to symptom severity, new generation molecular diagnostics that measure IgE against individual food allergens provide clinicians and patients with more reliable symptom severity risk profiles. Molecular diagnostics also support establishing whether food sensitization originates directly from exposure to food or indirectly (cross-reactivity) from pollen sensitization. Epidemiological surveys have indicated that allergy to peach primarily originates from peach consumption in Europe, whereas in China it is the result of primary sensitization to mugwort pollen, in both cases mediated by an allergen molecule from the same family. Epidemiological surveys give insight into the etiology of food allergy, the size of the problem (prevalence), and the risk factors involved, which together support evidence-based strategies for prevention. Over the past decade, food allergy has increased in the affluent world. Economic growth and urbanization in upcoming economies are likewise expected to lead to increased prevalence of food allergies, sometimes to different foods due to dietary habits. Molecular allergology and biotechnology now offer the possibility to combat the increasing burden of food allergy by developing safe immunotherapies for food allergy, using hypoallergenic mutant recombinant molecules. The first clinical trials to evaluate such approaches are underway. Last but not least, the identification and clinical risk characterization of a more and more complete list of food allergens additionally provides the allergenicity risk assessment of genetically modified foods a firmer basis.

[Meta analysis of the nutrition intervention effect of Yingyangbao on infants and young children in China].

OBJECTIVE: To systematically review the nutritional effect of YYB on infants and young children in poor rural regions. METHODS: Medline, PubMed, Cochrane Library, CNKI and other sources of nutrition and health information were retrieved with the predetermined key words. The quality of the obtained literatures was evaluated with the criteria established in this study. RveMan 5.3 was used in the meta analysis. RESULTS: Thirteen groups of qualified data from nine YYB intervention studies were used. The results showed that YYB significantly increased the level of Hb (MD = 0.94, 95% CI 0.94-1.15, P < 0.01), reduced the prevalence of anemia (RR = 0.34, 95% CI 0.25-0.46, P < 0.01). YYB showed no significant effect on WAZ and HAZ, but significant increase of WHZ was demonstrated by the analytical data (MD = 0.42, 95% CI 0.19-0.65, P < 0.01). Additionally YYB intervention groups also showed the prevalence of underweight (RR = 0.53, 95% CI 0.32-0.88, P < 0.05). CONCLUSION: As an infant complementary food supplement, YYB improved the nutrition status of infants and young children including increased Hb level, declined anemia prevalence and wasting rate.

Safety evaluation of Se-methylselenocysteine as nutritional selenium supplement: acute toxicity, genotoxicity and subchronic toxicity.

The significant toxicity of selenium emphasizes the need to assess the health risk of various selenocompounds as nutritional supplements. Se-methylselenocysteine (SeMC) was recently reported to be more bioactive but the toxicological effects have not been sufficiently characterized. This study aimed to evaluate the safety of SeMC and provide the Acceptable Daily Intake (ADI) for its use in human diet. Our results demonstrated that SeMC, with the Median Lethal Dose (LD50) of 12.6 and 9.26mg/kg BW in female and male mice, was of high potent of health hazard under acute oral exposure, but a battery of tests including Ames test, micronucleus assay and mouse sperm malformation assay suggested that SeMC was not genotoxic. The repeated dose study indicated little systemic toxicity of SeMC at supernutritional levels (0.5, 0.7, 0.9mg/kg BW/day) after 90-day oral exposure. Importantly, the 95% lower confidence value of Benchmark Dose (BMDL) was estimated as 0.34mg/kg BW/day according to the elevated relative liver weight. The ADI for human was established at 3.4µg/kg BW/day. The results suggested greater safety of SeMC as a nutritional selenium supplement, but health risk needs to be further evaluated when SeMC is applied beyond this level to achieve cancer chemoprevention.

[Effect of vitamin E and selenium deficiency on esophageal tumorigenesis and its oxidative stress mechanism].

OBJECTIVE: To explore the effect of vitamin E (VE) and selenium (Se) deficiency on esophageal tumorigenesis and its oxidative stress mechanism. METHODS: 110 male F344 rats were randomly divided into 3 groups: VE/Se deficient group (group A), VE/Se normal group (group B) and control group (group C). Animals in group A and group B were subcutaneously injected with N-nitrosomethylbenzylamine (NMBzA) at the dosage of 0.35 mg/kg BW, 3 times per week for 5 weeks. Control group was given the solvent 20% DMSO as negative control. Animals in group A were fed with low-VE/Se diet (46IU/kg VE, 0.05 mg/kg Se), animals in group B and C were fed with normal diet (80IU/kg VE, 0.15 mg/kg Se). Animals were sacrificed to perform macroscopic observation and pathologic inspection at the 25th week of the experiment. Plasma VE level was determined by high-performance liquid chromatography, and Se level was determined by fluorescence method. Cell proliferation and DNA damage in esophagus were detected through immunohistochemistry of BrdU and 8-OH-dG, respectively. Glutathione peroxidase (GPX) and glutathione transferase (GST) activities in plasma, esophagus and liver were analyzed by using test kits. RESULTS: VE/Se levels of group A were significantly lower than those of group B, the later were slightly lower than those of group C. Visible tumor incidence, tumor multiplicity and pathologic lesions in group A were all significantly more than those in group B. Comparing with group B, cell proliferation and 8-OH-dG levels were also significantly increased in group A. GPX and GST activities in plasma, esophagus and liver of group A were significantly higher than those of group B. CONCLUSION: Vitamin E and selenium deficiency significantly promoted the NMBzA-induced esophageal tumorigenesis. Oxidative stress and DNA damage may be one of the critical routes by which NMBzA induces carcinogenesis in rat esophagus.

Time-selective chemoprevention of vitamin E and selenium on esophageal carcinogenesis in rats: the possible role of nuclear factor kappaB signaling pathway.

Previous human intervention trial demonstrated that vitamin E (Ve) and selenium (Se) supplementation decreased esophageal cancer deaths among younger participants, but may have no effect or produce an opposite effect among older ones. In our study, we intended to mimic this human nutritional trial to determine the chemopreventive effects of Ve/Se supplementation at the early or late stage of esophageal carcinogenesis in rats. Esophageal squamous cell carcinoma (ESCC) was induced in Fischer 344 rats with N-nitrosomethylbenzylamine (NMBzA, 0.35 mg/kg BW, s.c., three times per week for 5 weeks). The rats were maintained on a modified AIN-93M diet with low levels of Ve/Se or supplemented with high levels of Ve/Se at different stages. At Week 25, the number and volume of visible tumors, the numbers of dysplasia and ESCC were significantly lower in rats of supplementation during the early stage (Group C) or during the entire experimental period (Group E), but not during the late stage (Group D). Ve/Se supplementation at the early stage also significantly decreased cell proliferation, nuclear factor kappaB (NFκB) activation, protein and mRNA expression of cyclooxygenase 2 and 5-lipoxygenase and biosynthesis of prostaglandin E2 and leukotriene B4 during the carcinogenesis of rat esophagus. Our results demonstrated that the chemopreventive efficacy of Ve/Se supplementation on NMBzA-induced esophageal cancer is time selective and that supplementation during the early stage is clearly effective but probably ineffective during the late stage of carcinogenesis. NFκB signaling pathway activation and aberrant arachidonic acid metabolism might be the underlying mechanism.

Evaluation of the in vitro and in vivo genotoxicity of almond skins.

OBJECTIVE: It aims to study potential genotoxicity of almond skins. METHODS: A bacterial reverse mutation assay was performed on S. typhimurium strains TA97, TA98, TA100, TA102, and TA1535 in the absence or presence of S-9 mixture at a dose range of 312.5 to 5 000 µg/plate. A micronucleus test and a mammalian bone marrow chromosome aberration tests were performed in Swiss Albino (CD-1) mice at doses of 625, 1 250, and 2 500 mg/kg bw used. RESULTS: Almond skins exerted no mutagenic activity in various bacterial strains of Salmonella typhimurium in either the absence or the presence of metabolic activation at all doses tested. Various doses of almond skins did not affect the proportions of immature to total erythrocytes, the number of micronuclei in the immature erythrocytes, or the number of structural and numerical chromosomal aberrations of Swiss albino mice. CONCLUSION: Almond skins are not genotoxic under the conditions of the in vitro bacterial reverse mutation assay and two in vivo tests - micronucleus test and mammalian bone marrow chromosome aberration test, which supports the safety of almond skins for dietary consumption.

Chemopreventive effects of early-stage and late-stage supplementation of vitamin E and selenium on esophageal carcinogenesis in rats maintained on a low vitamin E/selenium diet.

Low vitamin E and selenium (Ve/Se) nutritional status is known to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). A previous human intervention trial demonstrated that Ve/Se supplementation decreased the occurrence of esophageal cancer death among younger participants but not among older ones. In this study, we intended to mimic this human nutritional status to determine the chemopreventive effects of Ve/Se supplementation at the early or late stage of esophageal carcinogenesis in rats maintained on a low Ve/Se diet. ESCC was induced in F344 rats with N-nitrosomethylbenzylamine (NMBzA) (0.35 mg/kg body wt, subcutaneously, three times per week for 5 weeks). The rats were maintained on a modified AIN-93M diet with low levels of Ve/Se or supplementation to the normal level by using the AIN-93M diet. At Week 25, the numbers of visible tumors and ESCC were significantly lower in rats on AIN-93M diet during the entire experimental period (Group D) or during the early stage (Group B) but not during the late stage (Group C). Ve/Se supplementation (switching from the low Ve/Se diet to the AIN-93M diet) also decreased cell proliferation, angiogenesis, 8-hydroxy-2'-deoxyguanosine, biosynthesis of prostaglandin E2 and leukotriene B4, expression of cyclooxygenase 2 and 5-lipoxygenase in the esophagus. Our results demonstrated that Ve/Se supplementation inhibited NMBzA-induced esophageal carcinogenesis in rats on low Ve/Se diet, and supplementation during the early stage is more effective than during the late stage of carcinogenesis.

Almond consumption reduces oxidative DNA damage and lipid peroxidation in male smokers.

Smoking increases the risk of several chronic diseases associated with elevated oxidative stress status. Almonds are a good source of antioxidant nutrients and may diminish smoking-related biomarkers of oxidative stress. We investigated whether almond consumption decreases biomarkers of oxidative stress in young male smokers. We conducted a randomized, crossover clinical trial with 60 healthy male soldiers (18-25 y) who were habitual smokers (5-20 cigarettes/d) and supplemented their diet with 84 g almonds or 120 g pork (to control for calories) daily for 4 wk with a 4-wk washout period between treatment periods. In addition, 30 healthy nonsmoking men were provided the same daily serving of pork as reference comparison. Blood and urine were collected and assessed for biomarkers of oxidative stress. Baseline values of urinary 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) and peripheral lymphocyte DNA strand breaks were significantly higher by 185, 64, and 97% in smokers than nonsmokers, whereas activities of plasma superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase were significantly lower by 15, 10, and 9%, respectively. After the almond intervention, serum alpha-tocopherol, SOD, and GPX increased significantly in smokers by 10, 35, and 16%, respectively and 8-OHdG, MDA, and DNA strand breaks decreased significantly by 28, 34, and 23%. In smokers, after almond supplementation, the concentration of 8-OHdG remained significantly greater than in nonsmokers by 98%. These results suggest almond intake can enhance antioxidant defenses and diminish biomarkers of oxidative stress in smokers.

Tea pigments induce cell-cycle arrest and apoptosis in HepG2 cells.

AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis. METHODS: HepG2 cells were seeded at a density of 5X10(5)/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bcl-2 and p21(WAF1) proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells. RESULTS: Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21(WAF1) protein and downregulation of Bcl-2 protein. CONCLUSION: Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.

Studies on BN rats model to determine the potential allergenicity of proteins from genetically modified foods.

AIM: To develop a Brown Norway (BN) rat model to determine the potential allergenicity of novel proteins in genetically modified food. METHODS: The allergenicity of different proteins were compared, including ovalbumin (OVA), a potent respiratory and food allergen, bovine serum albumin (BSA), a protein that is considered to have a lesser allergenic potential, and potato acid phosphatase (PAP), a non-allergenic protein when administered to BN rats via different routes of exposure (intraperitoneally or by gavage). IgG and IgE antibody responses were determined by ELISA and PCA, respectively. An immunoassay kit was used to determine the plasma histamine level. In addition, possible systemic effect of allergens was investigated by monitoring blood pressure. RESULTS: OVA provoked very vigorous protein-specific IgG and IgE responses, low grade protein-specific IgG and IgE responses were elicited by BSA, while by neither route did PAP elicit anything. In either routes of exposure, plasma histamine level in BN rats sensitized with OVA was higher than that of BSA or PAP. In addition, an oral challenge with BSA and PAP did not induce any effect on blood pressure, while a temporary drop in systolic blood pressure in few animals of each routes of exposure was found by an oral challenge with OVA. CONCLUSION: BN rat model might be a useful and predictive animal model to study the potential allergenicity of novel food proteins.

[Effects of tea polyphenols and tea pigments on apoptosis in HepG2 cell line].

OBJECTIVE: To investigate the effect of tea polyphenols and tea pigments on apoptosis in HepG2 cells. METHODS: HepG2 cells were seeded at a density of 5 x 10(5)/well in six-well culture dishes. The cells were then treated with 50 or 100 mg/L tea pigments and harvested at 48h by trypsinization. Agrose electrophoresis was applied to investigate DNA-LADDER, Bcl-2 and Bax protein expression were detected by Western blot. RESULTS: Tea polyphenols and tea pigments induced the appearance of DNA-LADDER; Western blot analysis demonstrated that Bcl-2 expression was significantly inhibited and the expression of Bax was significantly induced by tea polyphenols and tea pigments. CONCLUSION: Induction of apoptosis may be an important mechanism of cancer chemoprevention by tea.

[Effects of tea polyphenols and tea pigments on telomerase activity of HepG2 cells].

OBJECTIVE: This study is to investigate the effect of tea polyphenols and tea pigments on telomerase activity of human liver cancer cell line, HepG2 cells. METHODS: TRAP-PCR-ELISA was applied to investigate the telomerase activity. RESULTS: Telomerase was positive in tea polyphenols treated groups, tea pigments treated groups and blank control group. Telomerase activities (A(450 approximately 690) values) were 1.56 and 1.46 in 50 mg/L and 100 mg/L tea polyphenols-treated groups, 1.55 and 1.49 in 50 mg/L and 100 mg/L tea pigments-treated groups, respectively. The results showed that telomerase activity was significantly inhibited by tea polyphenols and tea pigments treatment as compared with the blank control group (A(450 approximately 690) = 2.11). CONCLUSIONS: Tea polyphenols and tea pigments could significantly inhibit telomerase activity of HepG2 cells, and telomerase activity may be a useful biomarker for cancer chemoprevention.

[Studies on cancer chemoprevention by tea pigments].

The present study was to investigate the chemopreventive effects of tea pigments. In vitro study showed that tea pigments induced QR activity and GST activity in Hep G2 cells. Three animal models were used to observe the preventive effects of tea pigments on liver cancer, colorectal cancer and oral cancer. Oral administration of 0.1% tea pigments increased GST activity in rat liver by 18%, and this increase was accompanied by the significant increase of GST 1-1, 1-2, and 3-3 protein expression in rat liver. Tea pigments inhibited the proliferating cell nuclear antigen labeling index (PCNA-LI), the expression of Bcl-2 protein and ras-p21 protein, and induced the expression of Bax protein in rat colorectal cancer. PCNA-LI, silver-stained nucleolar organizer regions (AgNOR) and epidermal growth factor receptor (EGFR) expression were also inhibited by tea pigments in hamster oral cancer. Our results suggested that tea pigments had chemopreventive effects on cancer, and the anti-cancer properties may be due to the activation of detoxifying enzymes such as QR and GST, the inhibition of cell proliferation and the induction of apoptosis.

Effects of tea on preneoplastic lesions and cell cycle regulators in rat liver.

The effects of tea polyphenols and tea pigments on rat liver precancerous lesions and some cell cycle regulators were studied. A modified Solt-Farber model in rats was established by multiple low-dosage of N-nitrosodiethylamine (NDEA) i.p. injections, followed by i.p. CCl(4) injection and partial hepatectomy. Sixty male Wistar rats were randomly divided into four groups: positive control group, two tea-treated groups, and negative control group. Rats in tea-treated groups were given tea polyphenols (0.1%) and tea pigments (0.1%) in drinking fluid during the whole experiment. The number and area of glutathione S-transferase P (GST-P)-positive foci in the rat liver were used as biomarkers of precancerous liver lesions. Western blotting assay was carried out to detect the expression of cyclin D1, CDK4, and P21(WAF1/CIP1) on whole liver extract. At the end of the experiment (56 days), the number and area of GST-P-positive foci in liver increased significantly in carcinogen-administered positive control group, whereas no GST-P-positive foci were found in the negative control group in which animals did not receive carcinogen exposure. The number and area of GST-P-positive foci in tea-treated, carcinogen-exposed groups were significantly reduced as compared with the positive control group. It was also found that the expression of P21(WAF1/CIP1) was significantly induced and the expression of cyclin D1 and CDK4 was significantly inhibited in tea-treated groups. These results suggest that tea polyphenols and tea pigments are effective in preventing the precancerous liver lesions in rats, and modulation of cell cycle by regulating cell cycle regulators may be a possible mechanism.