• Title/Summary/Keyword: carcinogenic molecular

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Identification of Potential Carcinogenic Biomarker Following Exposure to N-ethyl-N-nitrosourea in Mice

  • Lim, Jung-Sun;Jeong, Sung-Young;Hwang, Ji-Yoon;Cho, Kyu-Hyuk;Cho, Jae-Woo;Han, Sang-Seop;Song, Chang-Woo;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.1 no.2
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    • pp.106-110
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    • 2005
  • N-ethyl-N-nitrosourea (ENU), which is a toxin and a carcinogen, as well as a mutagen, has a variety of effects on mice. ENU induces point mutation in male germ cell. Number of mutant animals are developed with ENU treatment. However, potentiality ot ENU as a carcinogen is not fully understood, even though, mutagenicity of ENU is broadly studied, In the present study, the gene expression profiling and histopathological investigation of ENU treated mouse's liver and brain were investigated. Also, the expression patterns of cancer related genes in ENU-treated mouse were analyzed.

Effects of Ginseng and Salvia miltiorrhiza Extracts on the Mutagenicity of MNNG in Drosophila (Drosophila에서 인삼 및 단삼 추출물이 MNNG의 돌연변이원성에 미치는 영향)

  • Choi, Yung-Hyun;Chung, Hae-Young;Yoo, Mi-Ae;Lee, Won-Ho
    • YAKHAK HOEJI
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    • v.38 no.3
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    • pp.332-337
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    • 1994
  • Using germinal and somatic cell mutation assaying systems of Drosophila melanogaster, effects of Ginseng and Salvia miltiorrhiza extracts on the in vivo mutagenicity induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) were investigated. For these purpose, the attached-X method and the mwh/flr spot test system which are an X-linked lethal mutation and a somatic chromosome mutation assaying system, respectively, were used. In the induction of X-linked lethal mutations during the spermatogenesis, MNNG showed more actions in the sperm and spermatid stages, in which Ginseng and Salvia miltiorrhiza extracts had remarkable inhibitory effects than other stages. Ginseng and Salvia miltiorrhiza extracts reduced the mutagenicity by MNNG in the mwh/flr system, which reveal that they can inhibit gene mutation, deletion and mitotic chromosomal recombination. These results seem to suggest that Ginseng and Salvia miltiorrhiza extracts may exert their inhibitory effects to in vivo mutagenic and/or carcinogenic properties of DNA-damaging agents.

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Functional Roles of Long Non-coding RNA in Human Breast Cancer

  • Ye, Ni;Wang, Bin;Quan, Zi-Fang;Cao, San-Jie;Wen, Xin-Tian;Huang, Yong;Huang, Xiao-Bo;Wu, Rui;Ma, Xiao-Ping;Yan, Qi-Gui
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.5993-5997
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    • 2014
  • The discovery of long noncoding RNA (LncRNA) changes our view of transcriptional and posttranscriptional regulation of gene expression. With application of new research techniques such as high-throughput sequencing, the biological functions of LncRNAs are gradually becoming to be understood. Multiple studies have shown that LncRNAs serve as carcinogenic factors or tumor suppressors in breast cancer with abnormal expression, prompts the question of whether they have potential value in predicting the stages and survival rate of breast cancer patients, and also as therapeutic targets. Focusing on the latest research data, this review mainly summarizes the tumorigenic mechanisms of certain LncRNAs in breast cancer, in order to provide a theoretical basis for finding safer, more effective treatment of breast cancer at the LncRNA molecular level.

The Overview of the Importances of Tumor Suppressor p53 for Investigating Molecular Toxicological Mechanisms of Various Environmental Mutagens (다양한 환경변이원의 분자독성학적 메커니즘 연구에 있어서 항종양 인자 p53의 중요성 고찰)

  • Jung Hwa Jin;Ryu Jae-Chun;Seo Young Rok
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.321-326
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    • 2004
  • The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.

Behavior in Solution and Mixing Ratio-Dependent Binding Modes of Carcinogenic Benzo[a]pyrene-7,8-dione to Calf Thymus DNA

  • Jin, Biao;Han, Sung Wook;Lee, Dong Jin
    • Bulletin of the Korean Chemical Society
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    • v.35 no.10
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    • pp.3015-3020
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    • 2014
  • The behavior of benzo[a]pyrene-7,8-dione (BPQ) in aqueous solution and its interaction with native DNA was investigated using conventional absorption and linear dichroism (LD) spectroscopy. The appearance of a broad absorption maximum at long wavelengths and its proportional relationship to solvent polarizability suggested that BPQ adopts a aggregated state for all solutions examined. Disappearance of this absorption band at higher temperatures in aqueous solution also supported BPQ aggregation. When associated with DNA absorption spectral properties were essentially the same as that in aqueous solution. However, two isosbestic wavelengths were found in the concentration-dependent absorption spectrum of the BPQ-DNA complex, suggesting the presence of at least two or more DNA-bound BPQ species. Both species produced $LD^r$ spectra whose magnitude in BPQ absorption region is larger or comparable to that in the DNA absorption region, suggesting that the molecular BPQ plane is near perpendicular relative to the local DNA helical axis. Therefore, BPQ molecules are aligned along the DNA stem in both DNA-aggregated BPQ species.

The Role of Stem Cells and Gap Junctional Intercellular Communication in Carcinogenesis

  • Trosko, James E.
    • BMB Reports
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    • v.36 no.1
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    • pp.43-48
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    • 2003
  • Understanding the process of carcinogenesis will involve both the accumulation of many scientific facts derived from molecular, biochemical, cellular, physiological, whole animal experiments and epidemiological studies, as well as from conceptual understanding as to how to order and integrate those facts. From decades of cancer research, a number of the "hallmarks of cancer" have been identified, as well as their attendant concepts, including oncogenes, tumor suppressor genes, cell cycle biochemistry, hypotheses of metastasis, angiogenesis, etc. While all these "hallmarks" are well known, two important concepts, with their associated scientific observations, have been generally ignored by many in the cancer research field. The objective of the short review is to highlight the concept of the role of human adult pluri-potent stem cells as "target cells" for the carcinogenic process and the concept of the role of gap junctional intercellular communication in the multi-stage, multi-mechanism process of carcinogenesis. With these two concepts, an attempt has been made to integrate the other well-known concepts, such as the multi-stage, multi-mechanisn or the "initiation/promotion/progression" hypothesis; the stem cell theory of carcinogenesis; the oncogene/tumor suppression theory and the mutation/epigenetic theories of carcinogenesis. This new "integrative" theory tries to explain the well-known "hallmarks" of cancers, including the observation that cancer cells lack either heterologous or homologous gap junctional intercellular communication whereas normal human adult stem cells do not have expressed or functional gap junctional intercellular communication. On the other hand, their normal differentiated, non-stem cell derivatives do express connexins and express gap junctional intercellular communication during their differentiation. Examination of the roles of chemical tumor promoters, oncogenes, connexin knock-out mice and roles of genetically-engineered tumor and normal cells with connexin and anti-sense connexin genes, respectively, seems to provide evidence which is consistent with the roles of both stem cells and gap junctional communication playing a major role in carcinogenesis. The integrative hypothesis provides new strategies for chemoprevention and chemotherapy which focuses on modulating connexin gene expression or gap junctional intercellular communication in the premalignant and malignant cells, respectively.

Differential Gene Expression in Estradiol-3-Benzoate-Treated Liver and Chemically- Induced Hepatocellular Carcinoma

  • KIM , SEYL;KANG, JIN-SEOK;JANG, DONG-DEUK;LEE, KOOK-KYUNG;KIM, SOON-AE;HAN, BEOM-SEOK;PARK, YOUNG-IN
    • Journal of Microbiology and Biotechnology
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    • v.14 no.6
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    • pp.1286-1294
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    • 2004
  • In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

Clinical, Cytogenetic and CYP1A1 exon-1 Gene Mutation Analysis of Beedi Workers in Vellore Region, Tamil Nadu

  • Sundaramoorthy, Rajiv;Srinivasan, Vasanth;Gujar, Jidnyasa;Sen, Ayantika;Sekar, Nishu;Abilash, Valsala Gopalakrishnan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7555-7560
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    • 2013
  • Background: Beedi rollers are exposed to unburnt tobacco dust through cutaneous and pharyngeal route and it is extremely harmful to the body since it is carcinogenic in nature and can cause cancer during long exposure. This indicates that occupational exposure to tobacco imposes considerable genotoxicity among beedi workers. Materials and Methods: In the present study, 27 beedi workers and age and sex matched controls were enrolled for clinical, cytogenetics and molecular analysis. Clinical features were recorded. The workers were in the age group of 28-67 years and were workers exposure from 8-60 years. Blood samples were collected from workers and control subjects and lymphocyte cultures were carried out by using standard technique, slides were prepared and 50 metaphases were scored for each sample to find the chromosomal abnormalities. For molecular analysis the genomic DNA was extracted from peripheral blood, to screen the variations in gene, the exon 1 of CYP1A1 gene was amplified by polymerase chain reaction (PCR) and then screened with Single Strand Conformation Polymorphism (SSCP) analysis. Results: A statistically significant increase was observed in the frequencies of chromosomal aberrations in exposed groups when compared to the respective controls and variations observed in Exon 1 of CYP1A1(Cytochrome P450, family 1, subfamily A, polypeptide 1) gene. Conclusions: This study shows that, the toxicants present in the beedi that enter into human body causes disturbance to normal state and behavior of the chromosomes which results in reshuffling of hereditary material causing chromosomal aberrations and genomic variations.

Investigation of Pollution of Polycyclic Aromatic Hydrocarbons and Heavy Metals in Soil near Railway Rails (철도레일 부근 토양의 다환방향족 탄화수소 및 중금속 오염도 조사)

  • Choi, Hyun-Kyung;Yoon, In-Ju;Shin, Tae-Cheon;Kim, Young-Hun
    • Journal of Environmental Science International
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    • v.27 no.11
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    • pp.947-956
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    • 2018
  • Trains have been a major means of transport in Korea during these past decades. However, train facilities such as stations and repair shops are contaminated with organic and inorganic substances. There is a high probability of train facility contamination with polyaromatic hydrocarbons (PAHs). This study evaluated the PAH and heavy metal contamination of soil near railroads in the Kyungpook area. A total of 18 soil samples were collected from the railroads and analyzed for 16 PAHs and 6 heavy metal species. The contamination level of the top soil was found to be slightly higher than that of the subsoil for contamination with PAHs. The ratio of carcinogenic PAH concentration to the total PAH concentration was relatively high, with a maximum of 0.9. The toxicity equivalent (TEQ) of the PAHs were 500.6 ng/kg in the topsoil and 355.5 ng/kg in the subsoil. The ratio of low molecular PAHs (LPAHs) to high molecular PAHs (LPAHs) ranged from 6.7 to 29.5; this shows that contamination is primarily due to combustion of fuel rather than due to petroleum. The ratio of phenanthrene to anthracene and the ratio of fluoranthene to pyrene also show that contamination occurred due to combustion for transportation. The heavy metal contamination level was lower than the Korean standard, but higher than the background concentration; this indicates that the soil was affected by the operation of the railways.

Immunohistochemical Expression of O6-methylguanine-DNA Methyltransferase (MGMT) in Korean Patients with Non-Small Cell Lung Cancer. (한국인의 비소세포폐암종에서 O6-methylguanine-DNA methyltransferase (MGMT)의 발현도 분석)

  • Lee, Kyung-Eun;Hong, Young-Seoub;Choi, Phil-Jo;Roh, Mee-Sook
    • Journal of Life Science
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    • v.18 no.4
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    • pp.580-584
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    • 2008
  • $O^6-methylguanine-DNA$ methyltransferase (MGMT) is a DNA repair protein that protects cells against the carcinogenic effects of alkylating agents. The loss of MGMT expression was commonly known due to hypermethylation of CpG islands in its promoter region. We evaluated the expression of MGMT by immunohistochemistry in order to examine the relationship between loss of MGMT expression and clinicopathological characteristics in 74 Korean patients with non-small cell lung cancers. Loss of MGMT was detected in 25 (33.8%) of 74 cases. The loss of MGMT expression was frequently seen in the adenocarcinoma than in the squamous cell carcinoma (p=0.021). However, there was no significant differences between loss of MGMT expression and other clinicopathological characteristics, including age, gender, smoking status, tumor size, tumor T stage, and lymph node metastasis (p>0.05). In conclusion, loss of MGMT expression was related with the histologic type of lung cancer. Further methylation study of MGMT promoter is needed to evaluate the relationships with immunohistochemical expression of MGMT and to clarify the role of MGMT in lung cancer.