Journal of Environmental Pathology Toxicology and Oncology (J ENVIRON PATHOL TOX)

Publications in this journal

• Article: Jaggery protects hepatorenal injury induced by acute exposure to carbon tetrachloride in Wistar rats.

  Chandra Kant Sharma, Monika Saxena, Vinay Sharma
  Journal of Environmental Pathology Toxicology and Oncology 01/2013; 32(1):1-7.
• Article: Restoration of Brain Antioxidant Status by Hydroalcoholic Extract of Mimusops elengi Flowers in Rats Treated With Monosodium Glutamate.

  Nagakannan P, Shivasharan BD, Thippeswamy BS, Veerapur VP
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  ABSTRACT: Monosodium glutamate (MSG) is commonly used as a flavor enhancer in many countries. However, overconsumption of MSG has been reported to produce detrimental effects on several organs. It mainly affects the normal physiology and function of the brain and causes severe oxidative stress. Mimusops elengi Linn. traditionally is used in many countries as a brain tonic and to calm anxiety and panic attacks. The effect of standardized hydroalcoholic extract of M. elengi flowers (ME) was evaluated against MSG-induced oxidative stress and excitotoxicity in Wistar rats. Excitotoxicity was induced by intraperitoneal administration of MSG (2 g/kg) for 7 days, and ME (100 and 200 mg/kg) was administered for 3 days before and for 7 days with administration of MSG. Animals were evaluated for locomotor activity, and brain homogenates were estimated for the levels of antioxidants and nitrite. In animals treated with MSG, pretreatment with ME improved ambulatory behavior, reduced lipid peroxidation and nitrite levels, and restored the enzymatic and nonenzymatic antioxidant (glutathione, total thiols, glutathione-S-transferase and catalase) status to near-normal levels; these were altered in the MSG control animals. Altogether, this investigation demonstrates the neuroprotective effect of ME against excitotoxicity and oxidative stress induced by MSG, and the observed protective effect might be attributed to the potential antioxidant property of ME.
  Journal of Environmental Pathology Toxicology and Oncology 01/2012; 31(3):213-221..
• Article: Effect of Marine Mangrove Avicennia marina (Forssk.) Vierh Against Acetic Acid Induced Ulcerative Colitis In Experimental Mice

  C. L Victoria Rise, V. Vinod Prabhu, C. Guruvayoorappan
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  ABSTRACT: Ulcerative colitis (UC) and Crohn's disease (CD) are two conditions that have many features in common and are referred as inflammatory bowel disease (IBD). Patients with IBD are predisposed to colorectal cancer (CRC). The present investigation evaluates the effect of marine mangrove Avicennia marina against acetic acid induced colitis. The treatment of A. marina extract significantly decreased the colonic lipid peroxides (LPO), glutathione peroxidase (GPx) and serum nitric oxide (NO) and significantly increased the colonic and erythrocyte superoxide dismutase (SOD) and glutathione (GSH) level compared to colitis control. In addition A. marina extract significantly decreased the lesion score and wet colon weight compared to colitis control. The treatment with A. marina extract reflects its therapeutic activity against UC by minimal damage of colonic epithelial cells compared to colitis control during histopathology examination. These protective role of A. marina extract against UC could be attribute due to the presence of higher content of decanoic acid, diethylhydroxylamine (DEHA), pentanoic acid, pyrrolidine, 4-chlorophenyl, thiazolidinones and arabinopyranoside (flavonoid). These findings suggest that A. marina extract could be useful as a potential (natural) therapeutic agent for IBD.
  Journal of Environmental Pathology Toxicology and Oncology 01/2012;
• Article: Black Tea Extract: A Supplementary Antioxidant in Radiation-Induced Damage to DNA and Normal Lymphocytes.

  Debjani Ghosh, Sandip Pal, Chabita Saha, Amit Kumar Chakrabarti, Salil C Datta, Subrata Kumar Dey
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  ABSTRACT: Myriad research has contributed significantly toward the understanding and identification of health benefits stemming from tea polyphenols and many other naturally occurring flavonoids present in fruits and vegetables. These flavonoids are known to mitigate reactive oxygen species-induced damage by scavenging them. In this study, hot-water black tea extract rich in flavonoids is evaluated as a supplementary antioxidant. The antioxidant efficacy of black tea extract was investigated by evaluating radioprotection conferred to pBR322 DNA, calf thymus DNA, and normal lymphocytes during gamma irradiation. The protection was measured by gel electrophoresis, fluorimetric study, cell viability assay, cytokinesis-blocked micronuclei assay, and comet assay. The 2,2-diphenyl-1-picrylhydrazyl scavenging ability of the tea extract used increased in a dose-dependent manner (IC50: 182.45 µg/mL). Positive correlation of radioprotection with antioxidant activity of black tea extract was observed in all systems. Maximum protection against radiation-induced damage was observed in pBR322 DNA and calf thymus DNA at ≥200 µg/mL of black tea extract. At a dose of black tea extract as low as 5 µg/mL, efficient radioprotection was observed in normal lymphocytes, which is encouraging and can be tested in the future as a natural antioxidant supplement during radiotherapy.
  Journal of Environmental Pathology Toxicology and Oncology 01/2012; 31(2):155-166.
• Article: Chromosomal aberrations in subjects exposed to ionizing radiation.

  Dubravka Jovicic, Snezana Milacic, Natasa Milic, Nenad Bukvic, Tanja D Vukov
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  ABSTRACT: Occupational exposure to low doses of ionizing radiation is a particularly delicate subject for investigation, due to the cumulative effects of chronic exposure. It is extremely important to consider and to measure the biological response to given conditions of exposure. The aim of this study was to establish possible recovery from DNA damage in subjects professionally exposed to radiation in their working area by examinations for chromosomal aberrations (CA) at two different times. The first group (I) was composed of 30 professionally exposed subjects in whom unstable CA (dicentrics, ring, acentric fragments, chromatid, chromosomal breaks, and chromatid interchanges) were identified at time zero. After removal from the radiation area, they were re-examined 9 months later. The second group (II) contained 64 healthy individuals, not professionally exposed to ionizing radiation or other known mutagenic agents. In the group of exposed individuals, five (16.67%) subjects exhibited permanent unstable CAs, even after 9 months absence from the radiation. When the nonexposed and exposed groups were compared, an increase of unstable aberrations (p < 0.05) was observed in the exposed group. Nevertheless, a statistically significant decrease of dicentrics, acentric fragments, and ring frequencies was observed in exposed individuals after 9 months away from the radiation area. However, chromatid and isochromatid break frequencies increased slightly but not significantly after 9 months. The detected CAs corresponded to the total effective doses of radiation measured in our subjects. The existence of CAs in some individuals even after absence from the radiation area suggests that the time necessary for the damaged DNA to recover is extremely variable and indicates interindividual differences in radiosensitivity as well as differences in the cellular-reparation response.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):75-82.
• Article: A paradox of cadmium: a carcinogen that impairs the capability of human breast cancer cells to induce angiogenesis.

  Stefania Pacini, Tiziana Punzi, Gabriele Morucci, Massimo Gulisano, Marco Ruggiero
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  ABSTRACT: Cadmium, a highly persistent heavy metal, has been categorized as a human carcinogen. Even though it is known that cadmium acts as estrogens in breast cancer cells, several studies failed to demonstrate whether cadmium is a causal factor for breast cancer. The lack of a strong association between cadmium and breast cancer could be found in the antiangiogenic properties of this heavy metal, which might counteract its carcinogenic properties in the progression of breast cancer. In this study, we exposed estrogen-responsive breast cancer cells to subtoxic levels of cadmium, and we evaluated their angiogenic potential using the chick embryo chorioallantoic membrane assay. Exposure of breast cancer cells to subtoxic levels of cadmium significantly inhibited the angiogenic potential of the breast cancer cell line, suggesting the possibility that cadmium might negatively regulate the production of proangiogenic factors in breast cancer cells. Our results suggest that cadmium might exert a paradoxical effect in breast cancer: on the one hand, it could promote carcinogenesis, and, on the other hand, it could delay the onset of tumors by inhibiting breast cancer cell-induced angiogenesis.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):85-8.
• Article: Modern concepts in the diagnosis and treatment of vitamin D deficiency and its clinical consequences.

  Richard Edlich, Allyson L Fisher, Margot E Chase, Carroll M Brock, K Gubler, William B Long
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  ABSTRACT: It is the purpose of this comprehensive report to outline a revolutionary strategy to prevent vitamin D deficiency in our nation. Vitamin D is a unique vitamin. Its metabolic product, calcitriol, is a profound secosteroid hormone that has impact on over 1000 genes in the human body. Recent clinical research has implicated vitamin D deficiency as a major factor in the etiology of rickets, a wide variety of cancers, as well as hypertension, stroke, heart attack, diabetes, bone fractures, periodontal disease, and even multiple sclerosis. There are two forms of vitamin D utilized in the human body: D2 and D3. Measurement of 25(OH)D is the most reliable method of detecting vitamin D deficiency. Several methods, including high-performance liquid chromatography (HPLC), chemoluminescence, and radioimmunoassay (RIA), have been developed for the measurement of total 25(OH)D levels. Prevention and treatment of vitamin D deficiency is accomplished by regulated sun exposure as well as vitamin D, supplementation. This information describing our plan to prevent vitamin D deficiency in the patients and employees of Legacy Health System is a landmark accomplishment that should be replicated in every healthcare setting in our country to prevent vitamin D deficiency.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):1-4.
• Article: Accelerated proteasomal activity induced by Pb2+, Ga3+, or Cu2+ exposure does not induce degradation of alpha-synuclein.

  Nurit Grunberg-Etkovitz, Nirit Lev, Debby Ickowicz, Almog Avital, Daniel Offen, Zvi Malik
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  ABSTRACT: The involvement of environmental heavy metals in Parkinson's disease (PD) has been suggested by epidemiologic studies; however, the mechanism of this effect is unknown. PD is characterized by the aggregation of alpha-synuclein in Lewy bodies. We previously showed that Pb2+ accelerates proteasomal activity. Therefore, we examined the effect of Pb2+, Ga3+, and Cu2+ on alpha-synuclein in human SH-SY5Y cells. The heavy metals induced an increase in heme-oxygenase-1 levels without significant cell death or ROS generation. The metals inhibited ALA-dehydratase, which is the inhibitory subunit of the proteasome, thereby accelerating proteasomal activity and decreasing protein levels of CDK-1 and PBGD. However, alpha-synuclein protein levels increased after exposure to metals, similar to the effect obtained with the proteasome inhibitor, hemin, suggesting that alpha-synuclein is inaccessible to proteasomal degradation. Indeed, electron microscopy revealed the formation of aggresomes in Pb2+- or hemin-treated cells. Thus, although heavy metals enhance proteasomal activity, alpha-synuclein is protected from degradation, and its protein levels and aggregation are increased.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):5-24.
• Article: The cyclooxygenase-2 inhibitor etoricoxib is a potent chemopreventive agent of colon carcinogenesis in the rat model.

  Manpreet Kaur Saini, Pinky Sharma, Jasmeet Kaur, Sankar Nath Sanyal
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  ABSTRACT: Cyclooxygenase-2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in several human cancers, including colon cancer, and therefore the potential ability of a selective COX-2 inhibitor, etoricoxib, is considered in the prevention of the 1,2-dimethyl hydrazine (DMH)-induced colon carcinogenesis in the rat model. DMH was injected s.c. for 6 weeks, whereas etoricoxib was fed orally to the rats on a daily basis. The results showed that DMH produced a very high number of multiple plaque lesions (MPLs), putative neoplastic biomarkers, localized throughout the colon, whereas considerable regression was observed with etoricoxib treatment. In addition, the etoricoxib group was the only group that exhibited very few of these lesions. Histopathological analysis revealed extreme dysplasia, a few adenomas, and other carcinogenic changes in the DMH group, which are distinctly absent in the etoricoxib-treated group. COX-2 was also seen to be highly expressed following DMH treatment. The DMH treatment caused very few apoptotic cells, as determined by the TUNEL assay of the colonic mucosa in paraffin sections whose number greatly increased following etoricoxib treatment. Because all these changes were clearly reversed by etoricoxib in DMH-treated animals, and the use of etoricoxib alone did not produce a neoplastic effect per se, it appears that etoricoxib, a selective COX-2 inhibitor, might be a safe and potentially chemopreventive agent in colon cancer.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):39-46.
• Article: Radioprotective effects of Aloe vera leaf extract on Swiss albino mice against whole-body gamma irradiation.

  Pradeep Kumar Goyal, Prashasnika Gehlot
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  ABSTRACT: The skin, being a cell-renewal system, is one of the first organs to be affected in total-body irradiation during radiotherapy. An attempt has been made in the present study to explore radiation-induced biochemical alterations caused by whole-body gamma irradiation and their modulation in Swiss albino mice by Aloe vera leaf extract (AVE). Mice were selected for this study from an inbreed colony and divided into four different groups: I (double-distilled water-treated group): considered as normal; II (Aloe vera-treated group): the animals were administered 1 g/kg body-wt/day Aloe vera leaf extract; III (radiation-treated group): the animals were exposed to 6 Gy gamma radiation at the dose rate of 0.96 Gy/min; and IV (combination group): animals were administered Aloe vera leaf extract continuously for 15 consecutive days, and on the 15th day they were irradiated to 6 Gy gamma radiation after 30 minutes of extract administration. The animals from the above groups were autopsied after 6 hours, 24 hours, and at 3, 7, 14, and 21 days of radiation. Biochemical estimations of DNA, lipid peroxidation, glutathione, catalase, and superoxide-dismutase were made. Total DNA, catalase, superoxide dismutase (SOD) activity in the skin, and glutathione (GSH) in the liver and blood significantly decreased compared to normal, but lipid peroxidation (LPO) in the liver and blood increased in the irradiated control group. In contrast, in experimental animals, DNA, catalase, and SOD in the skin and GSH in the liver and blood increased significantly, whereas LPO in the liver and blood decreased in comparison to irradiated control animals. Thus, Aloe vera leaf extract is found to have damage-resistant properties against radiation-induced biochemical alterations in Swiss albino mice.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):53-61.
• Article: Correlation of FBX dosimeter and micronucleus assay in radiation dosimetry of gamma chambers.

  Manjoor Ali, Prabha Tiwari, Amit Kumar, Kaushala Prasad Mishra, Badri Narain Pandey
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  ABSTRACT: The aim of the present study is to determine the dose distribution in gamma irradiation chambers by chemical dosimetry and to establish its correlation with biological dosimetry. The dose-distribution studies of these two gamma chambers show that compared to the center point of the chambers, the dose rate was 17%-22% higher at the circumference. Moreover, the dose rate was 12%-18% lower at the bottom and top positions compared to the center point. It was interesting to observe that the dose rate determined by chemical dosimetry was well correlated with the number of micro-nucleus (MN) formations at different positions of the chamber. Our results suggest that the formation of the single MN/cell was better correlated with the dose rate than the double MN/cell, suggesting that the number of single MN/cells could be better biomarkers for determining the dose rate. These results provide a correlation between chemical and biological dosimetry, which may have relevance in the development of better bioassay techniques for radiation exposure.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):63-73.
• Article: Siva-1 promotes K-48 polyubiquitination of TRAF2 and inhibits TCR-mediated activation of NF-kappaB.

  Radhika Gudi, John Barkinge, Sarah Hawkins, Bellur Prabhakar, Prasad Kanteti
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  ABSTRACT: The proapoptotic protein Siva-1 plays an important role in some of the extrinsic and intrinsic apoptosis signaling pathways in cancer cells. Previously, we showed that Siva-1 inhibited the activity of the prosurvival transcription factor NF-kappaB. In the present study, upon TCR cross-linking of Jurkat T leukemia cells, we demonstrated that the inhibitory target of Siva-1 is upstream of the IKK complex in the NF-kappaB signaling pathway. Additionally, Siva-1 also suppressed the activity of another crucial transcription factor AP-1, and a common mediator of both these pathways is the adaptor protein TRAF2. Further, we observed that Siva-1 indeed interacted with TRAF2 and negatively regulated its activity by promoting K48-hnked polyubiquitination. Siva-1 specifically interacted with the ring finger domain of TRAF2, which is essential for its E3 hgase activity and its ability to subsequently activate NF-kappaB. TCR cross-linking of Jurkat T cells that lacked Siva-1 revealed significantly lowered K48- but elevated K63-ubiquitinated TRAF2 levels upon TCR cross-linking, suggesting that the differential pattern of ubiquitination in these cells essentially contributed to a robust and sustained activation of NF-kappaB. The above results demonstrated an important role for endogenous Siva-1 in negatively regulating NF-kappaB activation by targeting TRAF2.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):25-38.
• Article: Revolutionary advances in the diagnosis and treatment of Familial Adenomatous Polyposis.

  Richard Edlich, Catherine L Cross, Courtney A Wack, Margot E Chase, K Gubler, William B Long
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  ABSTRACT: During the last 25 years, there have been revolutionary advances in the treatment of Familial Adenomatous Polyposis (FAP). The purpose of this article is to describe the pathophysiology, genetic testing, surveillance, surgical interventions, and psychosocial issues. The genetic defect in FAP is germline mutation in the adenomatous polyposis coli (APC) gene. Syndromes once thought to be distinct from FAP are now recognized to be part of the phenotypic spectrum of FAP. Syndromes with a germline mutation in the APC gene include FAP, Gardner syndrome, Turcot syndrome, and Attenuated Adenomatous Polyposis Coli (AAPC). FAP is a germline mutation in the APC gene with onset of florid polyposis in childhood and development of colorectal cancer by age 30. Colectomy is advised because of the high risk of developing colorectal cancer. AAPC is a variant of this condition with later age of onset and milder clinical phenotype. However, colectomy is advised once polyposis develops and polyps cannot be managed endoscopically. Despite the unique advances in genetic testing, psychosocial management of these syndromes remains to be a challenging problem.
  Journal of Environmental Pathology Toxicology and Oncology 02/2009; 28(1):47-52.
• Article: Effect of indoor air pollution from biomass fuel use on argyrophilic nuclear organizer regions in buccal epithelial cells.

  Nandan K Mondal, Anindita Dutta, Anirban Banerjee, Sreeparna Chakraborty, Twisha Lahiri, Manas Ranjan Ray
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  ABSTRACT: This study investigated the effect of indoor air pollution from biomass-fuel use on the expression of argyrophilic nucleolar organizer regions (AgNORs), an indicator of ribosome biosynthesis, in epithelial cells of oral mucosa. AgNORs were evaluated using cytochemical staining in 62 nonsmoking indian women (median age, 34 years), who cooked exclusively with biomass, and 55 age-matched women, who were from a similar neighborhood and cooked with relatively clean liquefied petroleum gas (LPG). Concentrations of particulate pollutants in indoor air were measured using a real-time aerosol monitor. Compared to the LPG-using controls, biomass-fuel users showed a remarkably increased number of AgNOR dots per nucleus (6.08 +/-2.26 vs 3.16 +/-0.86, p < 0.001), AgNOR size (0.85 +/-0.19 vs 0.53 +/-0.15 mum2, p < 0.001), and percentage of AgNOR-occupied nuclear area (4.88 +/-1.49 vs 1.75 +/-0.13%, p < 0.001). Biomass-using households had 2 to 4 times more particulate pollutants than that of LPG-using households. The changes in AgNOR expression were positively associated with PM10 and PM2.5 levels in indoor air after controlling for potential confounders such as age, kitchen location, and family income. Thus, biomass smoke appears to be a risk factor for abnormal cell growth via upregulation of ribosome biogenesis.
  Journal of Environmental Pathology Toxicology and Oncology 01/2009; 28(3):253-9.
• Article: Evaluation of Evidenced-Based Radioprotective Effi cacy of Gymnema sylvestre Leaves in Mice Brain

  K. V. Sharma, Umang Singh, Sharad Vats, K. I. Priyadarsini, A. L. Bhatia, Raka Kamal
  Journal of Environmental Pathology Toxicology and Oncology 01/2009;
• Article: Implementation of revolutionary legislation for informed consent for dental patients receiving amalgam restorations.

  Richard F Edlich, Catherine L Cross, Jill J Dahlstrom, William B Long, Anthony T Newkirk
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  ABSTRACT: Mercury is one of the most dangerous environmental toxins. Realizing the environmental dangers of mercury, the Norwegian Minister of the Environment and International Development, Erik Solheim, has therefore prohibited the use of mercury in products in Norway. This ban will include dental filling materials (amalgam) and measuring instruments, as well as other products. This ban is valid from January 1, 2008. Sweden announced a similar ban, and dentists in Denmark will no longer be able to use mercury in fillings after April 1, 2008. It is indeed unfortunate that the United States has not taken a leadership role in enacting Informed Consent Legislations for patients receiving dental amalgam restorations. Informed Consent Legislations have been enacted by Maine, California, Connecticut, and Vermont.
  Journal of Environmental Pathology Toxicology and Oncology 02/2008; 27(1):1-3.
• Article: Antioxidative effects of nonsteroidal anti-inflammatory drugs during the initiation stages of experimental colon carcinogenesis in rats.

  Shailender S Kanwar, Kim Vaiphei, Bimla Nehru, Sankar N Sanyal
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  ABSTRACT: The role of nonsteroidal anti-inflammatory drugs (NSAIDs) was studied on the antioxidant defense system and nitric oxide-derived damage in a 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Early precancerous lesions were established in the proximal and distal regions of the colon by morphological and histopathological examinations that were greatly regressed by the simultaneous treatment of the three NSAIDs, such as aspirin, celecoxib, and etoricoxib, along with the procarcinogen DMH. The intestinal brush border membrane (BBM) was isolated from the two regions and the colon-specific marker enzyme cysteine-sensitive alkaline phosphatase was assayed, which showed considerable elevation by DMH but reverted back to normal level by all the three NSAIDs. DMH also caused a higher level of lipid peroxidation as measured by malonyldialdehyde production, which was also found to be corrected by the NSAIDs, in both the region of the colonic tissue. The antioxidant activities were further established by a higher level of superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase in the NSAID treatment as compared to the DMH. The nonenzyme tripeptide, glutathione content was also recovered similarly as an antioxidant defense mechanism. To elucidate whether nitric oxide (NO) also plays an important role in the pathophysiology of colon cancer, the NO and citrulline levels were measured. The results show that the NO was lowered in DMH treatment and elevated by the administration of the NSAIDs while the citrulline level could not be recovered back. The findings of the present investigation indicate the chemopreventive modalities of the NSAIDs, particularly the COX-2 inhibitors.
  Journal of Environmental Pathology Toxicology and Oncology 02/2008; 27(2):89-100.
• Article: Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

  Bola Sadashiva Satish Rao, Dinesh Upadhya, Satish Kumar Adiga
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  ABSTRACT: The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (p<0.001) reduction in micronucleated binucleate cells (MNBNC%) after various doses of CDE treatment in V79 cells and HPBLs. The optimum dose of CDE (40 and 50 microg/ml in HPBLs and V79 cells, respectively) with the greatest reduction in micronuclei was further used in combination with various doses of gamma radiation (0.5, 1, 2, 3, and 4 Gy) exposed 1 h after CDE treatment. A linear dose-dependent MNBNC% increase in radiation alone group was observed, while 40/50 microg/ml CDE significantly resulted in the reduction of MNBNC%, compared to the respective radiation alone groups. CDE resulted in a dose-dependent increase in free radical scavenging ability against various free radicals, viz., 2, 2-diphenyl-2-picryl-hydrazyl (DPPH); 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE.
  Journal of Environmental Pathology Toxicology and Oncology 02/2008; 27(2):101-12.
• Article: Culture of human A375 melanoma cells in the presence of fibronectin causes expression of MMP-9 and activation of MMP-2 in culture supernatants.

  Aniruddha Banerji, Shamik Das, Amitava Chatterjee
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  ABSTRACT: Interactions between tumor cell surface integrin receptors and extracellular matrix (ECM) ligands play an important role in tumor development, affecting cell survival, proliferation, and migration. Integrin-ECM ligand interaction leads to phosphorylation of focal adhesion kinase (FAK) and activation of mitogen-activated protein kinase (MAPK) pathways. It has been reported that integrins also regulate expression and function of matrix metalloproteinases (MMPs). In this present work, we cultured human A375 melanoma cells in the presence of fibronectin to study fibronectin-integrin mediated modulation of MMP activity. A375 cells were cultured in serum-free culture medium (SFCM) in the presence of fibronectin (25 microg/0.75 ml), SFCM was collected and gelatin zymography was performed. Western blot and RT-PCR were performed with A375 cells cultured in the presence of fibronectin. Culture of A375 cells in the presence of fibronectin led to expression of MMP-9 and activation of MMP-2 within 2 h. When cells were treated with ERK inhibitor (PD98059) or PI-3K inhibitor (LY294002) and grown in the presence of fibronectin, MMP-9 expression and MMP-2 activation was inhibited. Tyrosine phosphorylation of FAK and ERK were increased in A375 cells grown in the presence of fibronectin. Increased MMP-9 mRNA expression and processing of MT1-MMP were also observed in A375 cells grown in the presence of fibronectin. Our findings indicate culture of A375 cells in SFCM in the presence of fibronectin perhaps generates a signaling cascade that leads to expression of MMP-9 and activation of MMP-2 in culture supernatants within 2 h. The signaling pathway activated is probably the FAK/ERK pathway.
  Journal of Environmental Pathology Toxicology and Oncology 02/2008; 27(2):135-45.