• Molecular & Cellular Toxicology
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• 제1권2호
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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.

• 약학회지
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• 제38권3호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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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.

• Environmental Analysis Health and Toxicology
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• 제19권3호
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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.

• Bulletin of the Korean Chemical Society
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• 제35권10호
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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.

• BMB Reports
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• 제36권1호
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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.

• Journal of Microbiology and Biotechnology
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• 제14권6호
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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).

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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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.

• 한국환경과학회지
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• 제27권11호
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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.

• 생명과학회지
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• 제18권4호
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• pp.580-584
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• 2008

본 연구에서는 손상된 DNA를 수복하는 중요한 효소로 알려진 $O^6-methylguanine-DNA$ methyltransferase (MGMT)발현의 의미를 비소세포폐암종에서 면역조직화학 염색법으로 알아보고자 하였다. 동아대학교 의료원에서 2001년부터 2004년까지 외과적으로 적출한 폐암종 조직 중 비소세포암종으로 진단된 74예를 연구대상으로 하였다. 면역염색 결과, MGMT 발현은 총 74예 중 49예(66.2%)에서 양성을 보였으며, 25예(33.8%)에서 단백 소실을 보였다. 조직학적 유형에 따른 결과를 살펴보면, 편평세포암종은 8/39예(20.5%)에서 단백 소실이 보였고, 샘암종은 17/35예(48.6%)에서 단백 소실이 관찰되어 통계적으로 유의한 차이가 관찰되었다(p=0.021). 하지만 나이, 성별, 흡연유무, 종양 크기, T 병기 및 림프절 전이에 따른 유의한 차이는 관찰되지 않았다(p>0.05). MGMT 단백 발현 소실은 특히 promoter 메틸화와 연관되어 종양에서 관찰된다고 알려져 있으므로, 향후 연구에서는 비소세포폐암종의 MGMT 단백 소실에 대한 임상적 의의를 밝히기 위하여 promoter 메틸화 연구가 추가적으로 수행되어져야 될 것으로 사료된다.