• Title, Summary, Keyword: tumor promotion

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Studies on the activity of telomerase in the mouse skin carcinogenesis (마우스피부암 발생과정에 있어서 텔로머레이저 활성에 관한 연구)

  • Kang, Ho-Il;Jee, Sung-Wan;Kim, Ok-Hee
    • Environmental Mutagens and Carcinogens
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    • v.25 no.2
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    • pp.66-70
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    • 2005
  • Telomerase, a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes, has activity in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. Although telomerase is known to be a regulated enzyme, the factors and mechanisms involved in telomerase regulation are not well understood. In the present study, we compared the effect of 12-O­tetradecanoyl-phorbol-13-acetate (TPA) and non-phorbol ester tumor promoters such as okadaic acid, anthralin and benzoyl peroxide on the expression of telomerase in the mouse skin carcinogenesis system, a well characterized model for studying pre-malignant and malignant progression. We found that most early papillomas harvested after 10 weeks of TPA promotion showed telomerase activity. Other papillomas harvested after 10 weeks of okadaic acid, anthralin and benzoyl peroxide promotion and after single treatment of DMBA only also showed telomerase activity, respectively. On the other hand, normal and all skins surrounded by papillomas harvested after 10 weeks of these promoters has no telomerase activity. Taken together these results, there appears to be no clear association between the level of telomerase activity and protein phosphorylation in mouse skin papillomas and telomerase may be useful as bio-markers in early detection of tumors.

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Effect of High Fat Diet and Calorie-restricted Diet on Protein Kinase C Activity in Mouse Epidermal Cell (고지방식이와 열량제한식이가 백서상피세포의 Protein Kinase C 활성에 미치는 영향)

  • Choe, Myeon
    • Journal of Nutrition and Health
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    • v.24 no.3
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    • pp.149-156
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    • 1991
  • To determine the effect of dietary fat and calorie level on protein kinase C(PKC) activity in mouse epidermal cells, female BALB/C mice (4weeks of age) were placed on high (24.6% ), moderate(5%) fat or calorie-restricted diets for at least 4 weeks. Diets were formulated on a nutrient/kcal basis such that the mice consumed the same amounts of protein. vitamins, minerals and fiber per kcal. PKC was assayed by the procedure of Wise et at. An apparent increase of PKC activity was observed from the aminal fed high fat diet when compared with the aminal fed moderate fat diet. PKC activity was decreased 40% by calorie restriction. In summary levels of dietary fat may contribute to mechanism of tumor promotion by increasing PKC activity in the mouse skin model.

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Macrophages Promote Coal Tar Pitch Extract-induced Tumorigenesis of BEAS-2B Cells and Tumor Metastasis in Nude Mice Mediated by AP-1

  • Zhang, Peng;Jin, Yue-Fei;Zhang, Qiao;Wu, Yi-Ming;Wu, Wei-Dong;Yao, Wu;Wu, Yong-Jun;Li, Zhi-Tao;Zhao, Yong;Liu, Yu;Feng, Fei-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4871-4876
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    • 2014
  • Background: We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. Materials and Methods: BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Results: Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. Conclusions: TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.

Induction of Apoptosis by Ursolic Acid in F9 Teratocarcinoma Cells (F9 기형암종세포에서 Ursolic acid의 apoptosis 유도기작)

  • 강창모;백진현;김규원
    • Journal of Life Science
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    • v.8 no.1
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    • pp.51-59
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    • 1998
  • The apoptosis-inducing activity of ursolic acid (UA) was examined in mouse F9 teratocarcinoma cells on the bases of biochemical and morphological characteeristics. UA, pentacyclic trierpene acid, exhibits antitumor activities including inhibition of skin tumorigenesis, induction of tumor cell differentiation and antitumor promotion. Treatment with UA showed that the decrease of cell viability was dose-dependent. UA also induced genomic DNA fragmetation, a hallmark of apoptosis, indicating that the mechanism of UA-induced F9 cell death was through apoptosis. When the morphology of the F9 cells was examined by electron microscopy, the cells treated with UA showed the charcteristic morphological features of apoptosis such as chromatin condensation and nuclear fragmentation. DNA fragmentations by UA were inhibired by cycloheximide, which suggest that de novo protein synthesis was required for DNA fragmentation by UA. Inaddition, the expression of c-jun was increased, but those of c-myc and laminin B1 were decreased during apoptosis induced by UA in F9 cells. These results suggest that UA causes an apoptosis in F9 cells. Further, the increased expression of c-jun may be involved in the UA-induced apoptosis of f9 cells.

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Quantitative Approaches to Assess Key Carcinogenic Events of Genotoxic Carcinogens

  • Fukushima, Shoji;Gi, Min;Fujioka, Masaki;Kakehashi, Anna;Wanibuchi, Hideki;Matsumoto, Michiharu
    • Toxicological Research
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    • v.34 no.4
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    • pp.291-296
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    • 2018
  • Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts ${\ll}$ Mutations ${\ll}$ GST-positive foci (preneoplasia) ${\ll}$ Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.

AN EXPERIMENTAL STUDY ON THE CHEMOPREVENTIVE EFFECT OF CHLOROPHYLLIN IN HAMSTER CHEEK POUCH TUMOR INDUCED BY 7, 12-DIMETHYLBENZ[A]ANTHRACENE (7, 12-dimethylbenz[a]anthracene(DMBA)로 유발된 햄스터 협낭암에서 chlorophylln의 암예방효과에 관한 실험적 연구)

  • Yoon, Kyu-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.2
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    • pp.137-145
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    • 2000
  • Carcinogenesis is a multi-stage process that generally consists of at least three steps; initiation, promotion, and progression. If one of these carcinogenic steps were suppressed or delayed, the cancer could be prevented. Cancer chemoprevention is defined to be inhibition or reversal of the carcinogenic process by the specific chemical agents and is a novel approach to cancer management alternative to conventional chemotherapy. Chlorophylln(CHL), a water-soluble derivative of chlorophyll, containing sodium and copper, has been known to be strong antimutagen in several test systems, but its mechanism of antimutagenic action is unknown. In the present experiment, the possibility of CHL as chemopreventive drugs on 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch carcinogenesis was investigated by mutagenicity test, carcinogenicity test, and frequency or spectrum of H-ras mutations in the both of DMBA-induced and chlorophylln-pretreated-DMBA induced tumor by polymerase chain reaction and non-isotopic restriction fragment length polymorphism. The treatment of CHL reduced the yields and multiplicity of the 0.5% DMBA-induced tumor, 86% to 62.5% and $3.7{\pm}0.6$ to $1.4{\pm}0.3$, respectively. The occurrence of histidine revertant by $20{\mu}mole$ DMBA was inhibited 25.6 to 81.7% by 1 to $5{\mu}M$ CHL in a dose-dependent manner. The mutation rates of H-ras gene in DMBA-induced and CHL-pretreated-DMBA induced tumor were 96%, 94% of which the most mutations were in codon 12/13. These results suggest that CHL inhibits the carcinogenic action of DMBA by the formation of complex between CHL and DMBA or the inhibition of the activation of DMBA in vivo. But CHL did not affect the mutation rates or its spectrum in already formed tumor.

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Treatment of Hemangiopericytoma-Associated Hypoglycemia with Glucocorticoid Therapy (전이성 혈관주위세포종 환자에서 발생한 저혈당을 프레드니솔론으로 치료한 1예)

  • Park, Sung-Woo;Kim, Dong-Geun;Kim, Myung-Jin;Jang, Hyo-Jin;Sohn, Se-Hoon;Koh, Sung-Ae;Lee, Ha-Young;Kim, Min-Kyoung;Lee, Kyoung-Hee;Hyun, Myung-Soo
    • Yeungnam University Journal of Medicine
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    • v.28 no.1
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    • pp.77-83
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    • 2011
  • Non-islet cell tumor-induced hypoglycemia (NICTH) is associated with mesenchymal tumor types, including hemangiopericytoma, fibrosarcoma, mesothelioma, and neurofibroma, as well as carcinoma of the liver, adrenal glands, and kidneys. Non- islet cell tumors induce hypoglycemia by overproducing an abnormal form of insulin-like growth factor II (IGF m. Complete removal of the tumor or reduction of the tumor mass is a successful therapeutic strategy in cases of NICTH. However, if the tumor re-grows, curative resection is nearly impossible, and hypoglycemia occurs repeatedly. Glucocorticoids are effective in terms of long-term relief from hypoglycemia through promotion of gluconeogenesis in the liver, tumor suppression, production of 'big'-IGF-II, and correction of the attendant biochemical abnormalities involving the growth hormone (GH)-IGF axis. We found that administration of corticosteroid therapy to a patient suffering from NICTH resulted in improvement of hypoglycemia associated symptoms.

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Differential Gene Expression after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in Hairless Mice Skin

  • Kang, Mi-Kyung;Kang, Ho-Il;Ryeom, Tai-Kyung;Eom, Mi-Ok;Park, Mi-Sun;Jee, Seung-Wan;Kim, Ok-Hee
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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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.

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Effect of Perilla Oil Rich in $\alpha$-Linolenic Acid on Colon Tumor Incidence, Plasma Thromboxane B2 Level and Fatty Acid Profile of Colonic Mucosal Lipids in Chemical Carcinogen-Treated Rats

  • Park Hyun Suh
    • Journal of Nutrition and Health
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    • v.26 no.7
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    • pp.829-838
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    • 1993
  • This study was designed to compare the effect of different dietary fats on the incidence of colorectal tumor, the level of plasma thromboxane B2(TXB2) and fatty acid profiles of platelet and colonic mucosal lipids in N - methyl - N - nitro - N - nitrosoguanidine(MNNG) - treated rats. Male Sprague Dawley rats, at 8 weeks old, were divided into 2 groups and infused intrarectally with saline(control group) or with 2mg MNNG(carcinogen-treated group) twice a week for 3 weeks. Each group was again divided into 4 groups and fed one of four diets(BT, CO, PO, FO) containing dietary fat at 9%(w/w) level for 37 weeks, Dietary fats were beef tallow(7.2%)+corn oil(1.8%) for BT, corn oil(9.0%) for CO, perilla oil(9.0%) for PO, fish oil (6.5%)+corn oil (2.5%) for FO diets. MNNG-treated rats had colonic tumor, while no tumors(adenocarcinoma and adenoma) than others. Tumor sizes in BT-MNNG rats ranged from 2mm papillary form to 15mm of polypoid. However, the size of tumors in PO-MNNG or FO-MNNG rats could not be measured by gross examination. BT-MNNG and CO-MNNG groups were higher in the level of plasma TXB2 and the ratio of c20 : 4/c20 :5 platelet. PO-MNNG groups were lower in the ratio of c20 : 4/c20 : 5(p<0.05) in fatty acid of colonic mucosal lipids suggesting that perilla oil and fish oil could reduce the level of PGE2 and TXB2 by modifying its precursor content and restrain tumor promotion in colon. Effect of perilla oil rich in $\alpha$-linolenic acid on colon carcinogenesis was similar to that of fish oil and thus perilla oil could have a protective effect against colon cancer possibly by inhibiting the production of arachidonic acid metabolite.

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