• Toxicological Research
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• 제14권4호
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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.

• BMB Reports
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• 제44권7호
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• pp.423-434
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• 2011

A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review.

• 한국식품저장유통학회지
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• 제21권3호
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• pp.301-307
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• 2014

본 연구 결과 울금 에탄올 추출물이 DMBA에 의해 유도한 유선 암화과정에서 종양의 발생률과 종양수를 감소시킴을 확인하였다. 이러한 종양세포의 증식 억제 효과는 울금의 암 예방 효과에 대한 기본 메커니즘 중 하나이다. 앞으로 효과적인 투여 경로 및 조직 특이성을 검토하기 위하여 더 많은 연구가 필요하다고 사료된다.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.222-229
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• 2009

Our previous finding that pre-initiation treatment of indole-3-carbinol (I3C) represents a chemopreventive effect in dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis has prompted us to test the global expression of genes at an early stage. Rats were continuously fed 300 ppm I3C in their diet at 6 weeks of age and were injected with DMBA at 7 weeks of age, and were sacrificed at 8 weeks of age. Global gene expression analysis using oligonucleotide microarrays was conducted to detect altered genes in DMBA- or DMBA plus I3C-treated mammary glands. Altered genes were identified by fold changes of 1.2 and by t-test (P<0.05) from the log ratios of the hybridization intensity of samples between control (Group 1) and DMBA (Group 2), and from those of samples between DMBA (Group 2) and DMBA plus I3C (Group 3). From these genes, we chose altered genes that were up- or down-regulated by DMBA treatment and recovered to the control level by I3C treatment. For early stage of carcinogenesis, I3C treatment induced the recovery to normal levels of several genes including cell cycle pathway (cyclin B2, cell division cycle 2 homolog A), MAP signaling pathway (fibroblast growth factor receptor 1, platelet derived growth factor receptor, beta polypeptide), and insulin signaling (protein phosphatase 1, regulatory (inhibitor) subunit 3B and flotillin 2), which were up-regulated by DMBA treatment. In addition, I3C treatment induced the recovery to normal levels of several genes including those of MAPK signaling (transforming growth factor, beta receptor 1 and protein phosphatase 3, catalytic subunit, beta isoform), which were down-regulated by DMBA treatment. These results suggest that the targeting of these genes presents a possible approach for chemoprevention in DMBA-induced mammary carcinogenesis.

• Genomics & Informatics
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• 제21권1호
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• pp.11.1-11.5
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• 2023

Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.39-40
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• 2001

The inhibition of carcinogenesis by tea has been demonstrated in animal models on many organ sites. These include cancers of the skin, lung, oral cavity, esophagus, stomach, liver, small intestine, pancreas, colon, bladder, prostate, and mammary glands. The most well studied sites are skin and lung.(omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.184-184
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• 2003

Endosulfan is one of the organochlorine pesticides, well-known endocrine disruptors (EDs). Many EDs show the estrogenic effect. Estrogen is a group of hormones that play an important role in mammary gland function and implicated in mammary carcinogenesis. In the present study. using mouse mammary gland organ culture (MMOC) system. we studied the the effects of endosulfan on nodule like alveolar lesion (NLAL) formation in the mouse mammary gland development. (omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Effects of Edible Phytochemicals and Their Synthetic Derivatives on Carcinogenesis and Mutagenesis
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• pp.15-15
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• 2001

In the present study, we examined the chemopreventive effects of indole-3-carbinol (I3C), a constituent of cruciferous vegetables (the Family of Cruciferae) such as cabbages, cauliflowers and broccoli on multiple intestinal neoplasia (Min) genetic mouse model and on mouse colon carcinogenesis induced by azoxymethane (AOM) as well as on rat mammary carcinogenesis induced by 7, 12-dimethybenz［$\alpha$］anthracene (DMBA).(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.58-58
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• 2001

In the present study, we examined the chemopreventive effects of indole-3-carbinol (I3C), a constituent of cruciferous vegetables (the Family of Cruciferae) such as cabbages, cauliflowers and broccoli on multiple intestinal neoplasia (Min) genetic mouse model and on mouse colon carcinogenesis induced by azoxymethane (AOM) as well as on rat mammary carcinogenesis induced by 7, 12-dimethybenz［$\alpha$］anthracene (DMBA).(omitted)

• Toxicological Research
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• 제16권4호
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• pp.275-284
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• 2000

The organ culture model of the whole mammary gland has many advantages for the study of branching morphogenesis and biological characteristics, including tumorigenesis. Prior to whole gland organ culture, rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA) or N-methyl-N-nitrosourea (MNU) for one week. The tramdorming effect and the morphological changes were assessed by the whole mount preparations and histopathological examination in terminal end buds (TEB), terminal ducts (TD), alveolar buds (AB), alveolar lobules (AL) and hyperplastic alveolar nodules (HAN) of the mammary gland. Grossfindings of the mammary glands at dissection were higher branching morphogenesis and larger volume in carcinogen-treated groups than in carcinogen-non-treated groups. Results of the whole mount method were coincided with those of the histopathological observations. Circular TEB, normally maintained AB, AL, and high cellular density were more frequently observed in carcinogen-treated groups than in carcinogen-nan-treated groups. Histopathologically, as a preneoplastic marker, HAN was maintained only in mammary organ culture of the carcinogen-treated groups. These findings suggest that in vivo trans-formation effects by carcinogens persisted during the mammary organ culture. These results were more characteristic in DMBA than in MNU-treated group. Ducts and terminal ducts appeared to have lost morphology during their growths in case of without diethylstilbestrol (DES). The fact that in vitro organ culture without DES was resulted in abnormal ductular morphogenesis confirms that DES is a physiological regulator of ductular epithelial cell growth.