• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.172-172
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• 2003

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototype of many halogenated aromatic hydrocarbons, is a ubiquitous, persistent environmental contaminant and displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic and tumor promoter. In this study, we investigated the tumor promotion effect of TCDD on the two-stage skin chemical carcinogenesis using hairless mouse (SKH1). We induced papillomas after treatment with N-methyl -N'-nitro-N-nitorsoguanidine (MNNG) as a initiator and TCDD as a promoter for 30 weeks. We found that the incidence or multiplicity of papillomas and hyperplastic nodules was maximally induced at MNNG-TCDD group compare to control, MNNG, and TCDD alone. These results suggesting that TCDD can acts as a potent promoter in the hairless mouse skin. In addition, we used cDNA microarray to detect the differential gene expression in normal, tumor surrounding, and tumor regions induced in hairless mouse skin by MNNG plus TCDD protocol. We found that 49 and 42 genes out of 5,592 genes associated with protein synthesis, cell organization, lipid transport and oxidative stress in tumor and surrounding regions were up- or down- regulated two fold or more, respectively. We are currently investigating how these genes play a role in TCDD-mediated chemical carcinogenesis.

• Korean Journal of Veterinary Pathology
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• v.5 no.1
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• pp.29-34
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• 2001

This study was conducted to assess the chemopreventive effects of chitosan in a rat colon carcinogenesis induced by azoxymethane (AOM). Ninety, 5-week-old, male F344 rats were divided into three groups. The animals in group 1 received subcutaneous injections of 15mg/kg AOM three times for two weeks, then were placed on powdered basal diet containing 2% chitosan for 37 weeks from weeks 3 to 40. The animals in group 2 were given AOM alone. The animals in group 3 were given 2% chitosan without prior carcinogen treatment. All animals were sacrificed at week 12 for quantitative analysis of aberrant crypt foci (ACF) and at week 40 fur analysis of tumor induction. Total numbers of ACF and AC per colon of group 1 were not significantly different from those of group 2. Tumor incidences and multiplicities of small intestine in the group 1 were significantly decreased compared with those of the group 2 (P<0.05). According to pathological diagnoses, adenocarcinoma incidence and multiplicity in the small and large intestine in the group 1 were significantly decreased compared with those of the group 2 (p<0.05). No toxic effects were observed in animals given chitosan in terms of body weights, and liver or kidney histology. These results indicate that chitosan may have a potential as chemopreventive agents of colon carcinogenesis during the postinitiation stage.

• Nutritional Sciences
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• v.4 no.2
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• pp.73-78
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• 2001

This study investigated the effect of different dietary fats and fibers on colon tumor incidence and cell proliferation, the levels of eicosanoids and polyamines in colonic mucosa of DMH-treated rats. The experiment was conducted on male Sprague Dawley rats using a 2 $\times$3 factorial design with two fats (corn oil and DHA-rich fish oil) and two fibers (cellulose and pectin) and a fiber-free control. The rats were find an experimental diet containing 15% (w/w) dietary fat and 6% (w/w) fiber for 25 weeks. Tumor incidence was Bower in rats fed fish oil as opposed to corn oil. The levels of arachidonic acid (AA) and eicosanoids ($PGE_2, and TXB_2$) in normal colonic mucosa were significantly lower in rats fed fish oil and there was a concomitant increase of docosahexaenoic acid (DHA). The levels of eicosanoids and AA in tumor tissues were significantly higher than those of normal colonic mucosa. The level of polyamines in normal colonic mucosa was not affected by dietary fats but was significantly lower than that in rumor tissues. Dietary fiber did not have a significant effect on rumor incidence and the levels of AA, eicosanoids and polyamines. Overall, fish oil rich in DHA reduced cell prolifiration and thus inhibited colon carcinogenesis through its effect on the distribution of AA and production of eicosanoids in normal colonic mucosa. However, its effect on colon carcinogenesis revealed a lack of consistency depending on the type of dietary fiber in diet.

• Nutritional Sciences
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• v.6 no.3
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• pp.160-166
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• 2003

To examine the evidence that wheat bran is protective against breast cancer development and that its main mechanism of action is by modulating estrogen metabolism. This review explores the role of different experimental factors on the anticancer effects of wheat bran and the relationship of changes to estrogen metabolism by wheat bran on breast cancer risk The timing of the experimental diets in relation to carcinogen administration, the length of feeding of the experimental diets, and the level of dietary fat had an impact on the effectiveness of different doses of wheat bran in reducing breast carcinogenesis. Wheat bran supplementation resulted in significant reductions in human plasma estrogen levels but not in that of animals tested. The change in excretory metabolism of estrogen by wheat bran feeding in animals was not related to any of the tumor indices measured. The protective effect of wheat bran in breast carcinogenesis is greatest at the promotional phase and when supplemented in a high fat diet. Doses of wheat bran in the 9-12% range in diet have been consistently protective. The inconsistency observed with higher doses of wheat bran may be dependent on the animal model used. Although wheat bran's inhibitory effects on tumor growth may involve changes to estrogen metabolism, the fiber and phytochemical components of wheat bran may also act through estrogen-independent mechanisms. For a better understanding of the effect of wheat bran on breast carcinogenesis, studies comparing the effects of different wheat bran components both alone and in combination need to be performed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6803-6812
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• 2015

Caveolin-1 is a 22-kD trans-membrane protein enriched in particular plasma membrane invaginations known as caveolae. Cav-1 expression is often dysregulated in human breast cancers, being commonly upregulated in cancer cells and downregulated in stromal cells. As an intracellular scaffolding protein, Cav-1, is involved in several vital biological regulations including endocytosis, transcytosis, vesicular transport, and signaling pathways. Several pathways are modulated by Cav-1 including estrogen receptor, EGFR, Her2/neu, $TGF{\beta}$, and mTOR and represent as major drivers in mammary carcinogenesis. Expression and role of Cav-1 in breast carcinogenesis is highly variable depending on the stage of tumor development as well as context of the cell. However, recent data have shown that downregulation of Cav-1 expression in stromal breast tumors is associated with frequent relapse, resistance to therapy, and poor outcome. Modification of Cav-1 expression for translational cancer therapy is particularly challenging since numerous signaling pathways might be affected. This review focuses on present understanding of Cav-1 in breast carcinogenesis and its potential role as a new biomarker for predicting therapeutic response and prognosis as well as new target for therapeutic manipulation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.521-525
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• 2012

Microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of numerous xenobiotics and is associated with several forms of cancer. Here, we investigated the role of mEH expression in bladder carcinogenesis, subsequent progression and recurrence. The expression of mEH was analyzed by Western blot in 50 bladder urothelial carcinoma and 20 normal epithelial tissues. There was a significantly higher mEH expression in the normal epithelium (P<0.05) and mEH expression was lower in high stage than in low stage tumors (P<0.05). Further, immunohistochmistry in 106 bladder urothelial carcinoma demonstrated mEH expression to be negatively correlated with histological grade, pT stage and recurrence (P<0.05). These findings suggest the important role of mEH in bladder carcinogenesis, cancer development and recurrence, providing support for efforts to develop mEH-based gene therapy.

• Journal of Environmental Health Sciences
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• v.36 no.1
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• pp.1-13
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• 2010

Evidences supporting gene-environment interaction are accumulating in terms of environmental exposure including lifestyle factors and related genetic variants. One form of defense mechanism against cancer development involves a series of genes whose role is to metabolize (activation/detoxification) and excrete potentially toxic compounds and to repair subtle mistakes in DNA. The purpose of this article is to provide a brief review of the notion of gene-environment interaction, environmental/occupational carcinogens and related cancers, and previous studies of gene-environment interaction on cancers caused by exposure to carcinogenesis. With a number of studies on the interaction between lifestyle factors (e.g., smoking and diet) and genetic polymorphisms in genes involved in xenobiotic metabolism and DNA repair excluded, only several studies have been conducted on the interactive effects between polymorphisms of CYPs, GSTs, ERCCs, XRCCs and environmental/occupational carcinogens such as vinyl chloride, benzo[a]pyrene, and chloroform on carcinogenesis or genotoxicity. Future studies may need to be conducted with sufficient number of subjects and based on occupational cohorts to provide useful information in terms of advanced risk assessment and regulation of exposure level.

• BMB Reports
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• v.43 no.10
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• pp.664-669
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• 2010

The present study aimed to investigate the membrane stabilizing effect of Thymoquinone (TQ) on cell surface glycoconjugates and cytokeratin expression against DMBA induced hamster buccal pouch carcinogenesis. 0.5% DMBA painting (three times per week) in hamster buccal pouches for 14 weeks resulted in the formation of well developed oral squamous cell carcinoma. We observed 100% tumor formation with marked abnormalities of glycoconjugates status in tumor bearing hamsters as compared to control animals. Oral administration of TQ at a dose of 30 mg/kg body weight, to DMBA painted hamsters on alternate days for 14 weeks, reduced the tumor formation as well as protected the levels of cell surface glycoconjugates in DMBA painted hamsters. The present study thus suggests that TQ has potent chemopreventive efficacy as well as protected the abnormalities on cell surface glycoconjugates during DMBA induced hamster buccal pouch carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1085-1091
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• 2014

Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9131-9136
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• 2014

ELDF15, homologous with AT2 receptor-interaction protein 1 (ATIP1), may play an important role in cell differentiation, proliferation, and carcinogenesis. We aimed to understand the biological function of ELDF15 via construction and transfection of a recombinant expression vector containing antisense ELDF15. Recombinant expression vectors were successfully constructed and transfected into K562 cells. A stable transfectant, known as pXJ41-asELDF15, stably produced antisense ELDF15. Compared with K562 and K562-zeo cells, K562-pXJ41-asELDF15 cells showed inhibition of cell proliferation. RT-PCR analysis showed that the expression and protein level of ELDF15 decreased significantly in K562 cells transfected with pXJ41-asELDF15. Expression of hemoglobin increased in K562 cells transfected with pXJ41-asELDF15 by benzidine staining. increases NBT reduction activity in K562 cells transfected with pXJ41-asELDF15.Colony forming efficiency in two-layer soft agar was clearly inhibited as assessed by electron microscopy. These results suggest that ELDF15 plays a potential role in cell differentiation, proliferation and carcinogenesis.