• Korean Journal of Veterinary Research
• /
• v.30 no.4
• /
• pp.447-457
• /
• 1990

In order to observe the distribution of mast cell on the stages of the mammary carcinogenesis, the numerical changes of mast cells in the mammary tumor development in rats treated with DMBA and compound 48/80 have been investigated by the light microscope. The results observed were summarized as follows: The appearance of tumor were not observed during the whole experimental period in the rats of the control group received injection of sterile saline, but tumors appeared in 100% of the animals, the tumor induction time that represented the number of days elapsing between the 3rd DMBA administration until a first tumor became $10{\times}10mm$ in diameter was $42.5{\pm}4.7$ days and the mean number of tumor masses per rat was $3.4{\pm}1.2$ in the DMBA treated group. And the majority of the DMBA-induced mammary neoplasms were appeared cervical mammary gland and thoracic mammary gland. The histological findings of mammary carcinoma were recognized adenocarcinoma in the DMBA treated group. Mast cells were distributed within the adipose tissues and the interglandular connective tissue in the control, but found to be randomly dispersed within the tumor cell masses, in the connective tissues adjacent to the periphery of the tumor, the adipose tissues and the subcutaneous tissues contiguous to the region of tumor development in the DMBA treated group. Numerical alterations of mast cells were observed in the mammary tumors that separated into three major classes of tumors: hyperplasia, atypical hyperplasia and carcinoma. The number of mast cells were distributed in the connective tissues adjacent to the mammary gland was $45.3{\pm}3.4$ cells in the control group, but was $50.2{\pm}4.9$ cells, $126.7{\pm}10.5$ cells and $340.3{\pm}19.2$ cells according to each stages of mammary tumorigenesis in the DMBA treated group.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
• /
• v.28 no.1
• /
• pp.245-259
• /
• 1998

Cellular transforming genes have been identified in a number of different tumor cell lines and tumor types. A significant number of these oncogenes belong to the ras gene family. The ras gene family consists of three closely related genes:H-ras, K-ras and N-ras which code for a related 21 kDa protein. Mutations in codon 12, 13 and 61 of one of the three ras genes convert these genes into acute oncogenes. The presence of H-ras gene mutations has important prognostic implications in various tumors. Each genomic DNA was isolated from tumors induced by implantation with DMBA, or by treatment with DMBA -implantation/irradiation. When genome DNA was transfected into NIH 3T3 cells and investigated by two-step PCR-RFLP, the fOllowing results were concluded: 1. Transformation foci developed in two groups when the genome DNA of two experimental groups were transfected into NIH 3T3 cells. 2. Transformation efficiency was 0.01-0.02 foci/㎍DNA in the experimental group with the DMBA-implantation, 0.01-0.03 foci/㎍lgDNA in the experimental group with the DMBA-implantation/irradiation according to results of transfection assay. 3. When the point mutation of H-ras gene was investigated by a two-step PCR-RFLP, there was 13.9％ (5/36) in the experimental group with the DMBA implantation, 15.4 ％ (6/39) in the experimental group with the DMBA -implantation/irradiation. 4. The point mutation in codon 12 and 61 of H-ras was 5.6％(2/36) and 8.3％(3/36) in the experimental group with the DMBA implantation. 5. The point mutation in codon 12 and 61 of H-ras gene was 7.7％(3/39) in the experimental group with the DMBA -implantation/irradiation.

• Environmental Mutagens and Carcinogens
• /
• v.18 no.1
• /
• pp.22-25
• /
• 1998

Anticarcinogenic activity of astaxanthin-containing egg yolks (designate AEY) was investigated for 7,12-dimethylbenz[a]anthracene (DMBA)-induced two stage mouse epidermal carcinogenesis. Female ICR mouse (6-7 weeks of age) were house in a humidity-and-temperature-controlled facility and subjected to feed and water ad libitum. AEY (10 mg/0.2 ml acetone) was painted on the back of mice 7 days, 3 days and 5 min before DMBA treatment (50 nmole/0.2 ml acetone). One week later after DMBA treatment, 6 ${\mu}g$ tetradecanoyl 12-phorbol 13-O-acetate (TPA) dissolved in 0.2 ml acetone was applied on the mouse twice weekly over a period of 22 weeks. No sample was given to control mice. Control egg yolk (CEY) and astaxanthin-containing oil (designate AO) from Phaffia rhodozyma were used as positive controls. Mouse treated with AEY exhibited 10 tumors per mouse whereas control mouse exhibited 15 tumors per mouse, the fact that 33% reduction of tumor per mouse by AEY treatment. Tumor incidence was also reduced to 15% by AEY treatment when compared to that of control group. Such effects were also seen in CEY and AO treatment groups, but leaser extent. AO gave reduction of food intake and body weights relative to those of AEY and CEY, indicating toxicity of AO. These results suggest that AEY exhibits anticarcinogenic activity for DMBA-induced mouse epidermal carcinogenesis.

• Toxicological Research
• /
• v.23 no.2
• /
• pp.135-142
• /
• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.

• Korean Journal of Veterinary Research
• /
• v.41 no.4
• /
• pp.549-555
• /
• 2001

Indole-3-carbinol (I3C), one component of cruciferous vegetables (the Fammily of Cruciferae), has been shown to exert its chemopreventive effect in liver, colon and mammary tissue before or concurrent exposure of carcinogen, but there have been several evidences that consumption of I3C induced tumor promotion in some tissues. Our studies were investigated to examine the modifying effects of I3C in the 7,12-dimethylbenz[$\alpha$]anthracene (DMBA) induced rat mammary gland tumor model. Fifty-two female Sprague-Dawley rats were randomly divided into five groups. Animals of the group 1 were given the diet containing 100ppm I3C and animals of the groups 2 and 4 were given the diet containing 300ppm I3C from 6 weeks of age. At 7 weeks of age, the animals of the groups 1, 2 and 3 were intubated with DMBA. All amimals were killed at 20 weeks after carcinogen treatment. There were significant increases of food consumption in I3C feeding groups compared with those of basal diet feeding groups. The incidences of the mammary tumors in the group 1, 2 and 3 were 75.0% (9/12), 56.3% (9/16) and 93.8% (15/16), respectively and the average number of tumors of group 1 (DMBA+I3C 100ppm: $2.08{\pm}0.61$) and 2 (DMBA+I3C 300ppm: $1.19{\pm}0.32$) were significantly lower than that of group 3 (DMBA alone: $4.63{\pm}0.72$) at the value of P<0.05 and P<0.001, respectively. In the pathological examination of appearing tumors, most of them were adenocarcinoma. Many epithelial cells of tumors showed strong estrogen receptor (ER) $\alpha$ expression but there were slight difference of ER $\alpha$ expression among the type of tumors. We suggest that pre-initiation treatment of I3C has an inhibitory effects on mammary carcinogenesis induced by DMBA.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5753-5757
• /
• 2012

Apoptosis, also known as cell suicide or programmed cell death, removes unwanted and genetically damaged cells from the body. Evasion of apoptosis is one of the major characteristic features of rapidly proliferating tumor cells. Chemopreventive agents inhibit or suppress tumor formation through apoptotic induction in target tissues. The aim of the present study was to investigate the pro-apoptotic potential of lupeol during 7,12-dimethylbenz(a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA three times a week for 14 weeks in the buccal pouches of golden Syrian hamsters resulted in oral squamous cell carcinoma. The expression pattern of apoptotic markers was analyzed using immunohistochemistry (p53, Bcl-2, Bax) and ELISA reader (caspase 3 and 9). In the present study, 100% tumor formation with defects in apoptotic markerexpression pattern was noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50mg/kg bw completely prevented the formation oral tumors as well as decreased the expression p53 and Bcl-2, while increasing the expression of Bax and the activities of caspase 3 and 9. The present study thus indicated that lupeol might inhibit DMBA-induced oral tumor formation through its pro-apoptotic potential in golden Syrian hamsters.

• Applied Microscopy
• /
• v.20 no.2
• /
• pp.102-116
• /
• 1990

To investigate the ultrastructural features of rat back skin tumor induced by 7, 12-Dimethylbenz[a]anthracene(DMBA), morphological changes during carcinogenesis were undertaken by the light and the electron microscopes. On the light microscopic levels, dysplasia was observed at the 6th week of treatment with 0.5% DMBA, hyperplasia at the 8th week, and carcinoma in sitv or invasive carcinoma at the 12th week. In addition to those characteristics, papillomatosis was observed at the 18th week. Under the electron microscopy, intercellular spaces were enlarged in the early phase. Nucleolar enlargement, the increase of free ribosomes, the condensation of tonofibrils, and the irregular arrangement of desmosomes appeared at the 6th week of application. Thereafter, the degradation of desmosomes and the discontinuity of basal lamina were characterized. And then, epidermal cell processes were protruded toward the connective tissue at the site of discontinuity of basal lamina at the 12th week. At the 14th to 18th week, DMBA-induced fibrosarcomas or papillomas were observed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2563-2569
• /
• 2012

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.27 no.5
• /
• pp.973-979
• /
• 1998

This study was conducted to investigate the effectiveness of pumpkin powder in the diet of experimental animals on chemically induced stomach and mammary canceers. Three weeks old male SpragueDawley rats were randomly allocated to either 1) basal diet+MNNG, 2) basal diet+MNNG+PMC, 3) 2.5% pumpkin powder supplemented diet+MNNG+PMC, or 4) 5.0% pumpkin powder supplemented diet+MNNG+PMC for stomach cancer experiment. And female Sprague-Dawley(5 weeks old) rats were randomly assigned to either 1) basal diet only, 2) basal diet+DMBA, 3) 2.5% pumpkin powder supplemented diet+DMBA, or 4) 5.0% pumpkin powder supplementd diet+DMBA. In both experiments, supplements of pumpkin powder in basal diet decreased body weight of both male and female experimental animals. Pumpkin powder in rat diet decreased significantly(p<.05) chemically induced stomach cancer. With its suppressing effects on stomach cancer, pumpkin powder in diet of experimental rats had decreasing effects on the initiation and development of DMBA-induced mammary cancer. In conclusiion, current study may provide in vivo data to develop health foods using pumpkin. Further studies, however, are essential to clarify the exact role of pumpkin powder in chemically induced stomach and mammary cancers.

• Korean Journal of Veterinary Pathology
• /
• v.3 no.2
• /
• pp.83-85
• /
• 1999

Weekly subcutaneous injection of7 ,12-dimethylbenz[a]anthracene(DMBA) at a dose level of 0.25kg/mg body weight induced proliferative lesions in the spleen of syrian golden of syrian In addition, subcutaneous tumors at injection sites were observed. The splenic lesions included stromal hyperplasia and hacmangioma-like lesion.