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

• Toxicological Research
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• v.9 no.1
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• pp.1-11
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• 1993

This study was carried out to investigate the immunopathological effects of 7, 12-Dimethylbenz[a]anthracene(DMBA) on mouse thymus. DMBA was administered subcutaneously to BALB/C mice by interscapular single injection of 50 or 100 ng/g of body weight. Each DMBA treatment group and additional corn oil control group of mice were studied on day 1, 3, 7, 14 and 21 following the injection of DMBA. DMBA treatment resulted in marked decreases in weights and cellularity of thymus. Thymus weights were decreased by 50.6 and 66.0% at 21 days, respectively, after treatment of 50ng/g and 100 ng/g DMBA.

• Food Science and Biotechnology
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• v.18 no.1
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• pp.245-248
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• 2009

Present study was investigated the hepatic effects of equol on the 7,12-dimethylbenz(a)anthracene (DMBA)-induced enzymatic activity and expression of CYP1A1 and CYP1B1 in mice. Equol was administered orally at 5 and 25 mg/kg BW for 4 weeks. Subsequently, mice pretreated with equol received DMBA intragastrically twice a week for 2 weeks. DMBA induced CYP1 activity as well as the expression of CYP1A1 and CYP1B1. Each of these effects was significantly reduced by equol in dose-dependent manner (p<0.05). Equol also reduced the relative AhR mRNA expression, similar to its effect on CYP1A1. These results suggest that equol modulates the CYP1A1 through a reduction of AhR expression in mice treated with DMBA.

• Toxicological Research
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• v.8 no.2
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• pp.179-189
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• 1992

This study was carried out to investigate the immunopathological effects of 7,12-Dimethylbenz[a]anthracene(DMBA) on spleen in mice. DMBA was administered subcutaneously to BALB/C mice by interscapular single injection of 50 or 100${\mu}g/g$ of body weight. Each DMBA treatment group and additional corn oil control group of mice were studied on day 1,3,7,14 and 21 following the injection of DMBA. DMBA treatment resulted in marked decrease in weights and cellularity of spleen. Spleen weights showed the greatest decrease at 14days after 50${\mu}g/g$ DMBA treatment, and at 21days after 100${\mu}g/g$ DMBA treatment. Spleen cellularity was similarly deceased in comparison with spleen weights. Spleen showed morphologically no typical changes throughout the experiment after 50${\mu}g/g$ DMBA treatment. Following the treatment of 100${\mu}g/g$ DMBA the spleen showed severe fibrosis, hemosiderin precipitation, and megakaryocytes decrease in red pulp at 14 days, while hemopoietic function was partly restored in addition to the appearance of a few megakaryocytes at 21 days. In spleen sections treated with antibodies to IgM or Thy1.2, lymphocytes strongly stained with IgM antibody were infiltrated around the central artery within the white pulp, and T-lymphocytes of periarterial lymphatic sheath (PALS) were diminished and destructed in sections treated with Thy1.2 antibody, at 14 days after the treatment of 100${\mu}g/g$ DMBA. By the electron microscopy phagocytic epithelial cells or macrophages were remarkably increased in spleen at 14and 21days following the treatment of 100${\mu}g/g$ DMBA.

• Toxicological Research
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• v.14 no.4
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• pp.465-474
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• 1998

This study was examined on the effect of ex-vivo immunotherapy in 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Sprague-Dawley female 40 rats were divided into Jour groups. As a positive control, Group I was intubated with DMBA, 5 mg /100 g body weight and single dose, at experimental onset. Group II was treated ex-vivo immunotherapy with polyinosinic-polycytidylic acid (Poly I : C) and Group III was treated with Interleukin-2 (IL-2). Group IV was negative control. All rats were sacrificed at 16 weeks after DMBA intubation. Mammary gland wet weight, dry fat free tissue weight, incidence of tumor, and the number of lobules, alveolar buds, terminal end buds, and terminal ducts were examined. Morphological changes of the mammary gland after treated with DMBA were analyzed by whole mount and histopathological method. As results, the induced mammary tumors of Group I, II and III were 60%, 33% and 0%, respectively. Histopathological types of induced-mammary tumors were adenoma, adenocarcinoma and carcinosarcoma. In analysis of the whole mount method, the number of the terminal end buds, terminal ducts and lobules were significantly lower in Group II (p<0.01) and III (p<0.01) than DMBA alone treated Group I. In microscopic observation, hyperplastic alveolar nodules were significantly lower in Group III than Group I (p<0.01). In conclusion, IL-2 had strong inhibitory effect on the mammary gland tumorigenesis induced by DMBA in rats. Whole mount method may be a useful technique to assess the mammary carcinogenesis. Moreover, hyperplastic alveolar nodules were very sensitive parameter to assess the mammary carcinogenesis.

• Applied Microscopy
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• v.20 no.2
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• pp.102-116
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• 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
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• v.13 no.6
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• pp.2563-2569
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• 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.

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

• 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.

• KSBB Journal
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• v.4 no.1
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• pp.8-10
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• 1989

Mutagenic characteristics deactivation of 7, 12-dimethylbenz(a)anthraracene was studied in a nonacclimated sandy loam soil at low and neutral pH soil conditions. Soil extracts containing transformation products were separated into three fractions based on HPLC retention time(polarity). Highly polar transformation products of 7, 12-dimethylbenz(a)anthracene demonstrated a negative mutagenic response with the Ames mutagenicity assay, strain TA-100, for both low and neutral pH soils. Moderate and low polar fractions, however, induced mutagenicity for both soil samples with mutagenic ratios similar to those of the parent compound.