• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
• /
• pp.151-151
• /
• 2001

According to the epidemiological studies in chromium workers, hexavalent chromium is associated with the risk of lung cancer. Reactive oxygen species produced by hexavalent chromium exposure may play an important role in the carcinogenesis process. We measured one kind of oxidative DNA damages, 8-hydroxydeoxyguanosine (8-OHdG) and its repair activities as an indicators of cellular oxidative stress in rat lungs by the repeated inhalation exposure to sodium chromate.(omitted)

• Archives of Pharmacal Research
• /
• 제22권5호
• /
• pp.474-478
• /
• 1999

Modulation of unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) after exposure to various chemical carcinogens was investigated in the primary rat hepatocytes. Unscheduled DNA synthesis was induced by treatment of such direct acting carcinogens as methly methanesulfonate (MMS) and ethyl methanesulfonate (EMS) or procarcinogens including benzo(a)pyrene (BaP) and 7, 12-dimethylbenz(a)anthracene (DMBA). Unscheduled DNA synthesis was determined by measuring [methyl-3H]thymidine radioactivity incorporated into nuclear DNA of hepatocytes treated with carcinogens in the presence or absence of DHEA. Hydroxyurea $(5{\times}10^{-3} M)$was added to growth medium to selectively suppress normal replication. DHEA at concentrations ranging from $(1{\times}10^{-6} M)$ to$(5{\times}10^{-4} M)$ did not significantly inhibit unscheduled DNA synthesis induced by either MMS $(1{\times}10^{-4} M)$ or EMS $(1{\times}10^{-2} M)$. In contrast, DHEA-significantly inhibited unscheduled DNA synthesis induced by BaP $(6.5{\times}10^{-5} M)$ and DMBA.$(2{\times}10^{-5} M)$. DHEA-induced hepatotoxicity in rats was examined using lactate dehydrogenase (LDH) release as an indicator of cytotoxicity. DHEA exhibit no significant increase in LDH release compared with the control at 18 h. These data suggest that nontoxic concentration of DHEA does not affect the DNA excision repair process, but it probably influence the enzymatic system responsible for the metabolic activation of procarcinogens and thereby decreases the amount of the effective DNA adducts formed by the ultimate reactive carcinogenic species.

• Archives of Pharmacal Research
• /
• 제11권3호
• /
• pp.225-229
• /
• 1988

A ginseng protein fraction which has been reported to have radiation protective effect was purified from Korean ginseng and its effects on relative survival and chromosome aberration were studied in UV irradiated CHO-K1 cells. When the protein fraction $(100\;{\mu}g/ml)$ was added to the cells before UV irradiation at 4\;J/$m^2$,, the survival rates were increased to 53.8% from 40.6% in control. Addition of the protein $(100\;{\mu}g/ml)$ after UV irradiation at 4 and $8\;J/m^2$ raised the rates to 85.4 and 24.0% from 79.2 and 11.5% in control, respectively. When the ginseng protein $(800\;{\mu}g/ml)$ was added to the cells exposed to UV light at 10, 20, $30\;J/m^2$, the frequencies of chromosome aberration (CA) were reduced significantly to almost same level regardless of the UV dose increment and there was no significant difference between pre- and post-treatment. When the concentration of ginseng protein was increased from 200 to $800\;{\mu}g/ml$, at UV dose of 10, 20, $30\;J/m^2$ each, the CA frequencies were decreased consistently as the dose of ginseng protein increased, at all UV doses tested. Similar effects were observed in both cases of pre- and post-treatment. The data suggest that the protein may reduce cell damage caused by UV light, especially damage to DNA molecule, or play a role in repair processes of damaged DNA, to increase cell survival and reduce chromosome aberrations.

• 한국환경성돌연변이발암원학회지
• /
• 제22권3호
• /
• pp.205-210
• /
• 2002

In irradiated human lymphocytes, translocation of chromosome has been more frequently observed than dicentric chromosome. Differences in the misrepair process leading to translocation and dicentric chromosomes may explain the above observations. In order to find out whether dicentric and translocation are originated from different mechanism, the frequencies of radiation induced translocation and dicentric in lymphocytes were examined following treatment of irradiated lymphocytes with two DNA repair inhibitors, 3AB for inhibition of poly(ADP-ribose) synthesis and Ara C for inhibition of DNA-polymerase $\alpha$. Ara C potentiated the frequencies of radiation induced dicentric and translocation. 3AB also potentiated the frequencies of radiation induced dicentric, but not translocation. These results suggest the potential differences in the mechanisms in the formation of translocation and dicentric chromosomes.

• Molecules and Cells
• /
• 제42권11호
• /
• pp.794-803
• /
• 2019

Ultraviolet light (UV)-induced cellular response has been studied by numerous investigators for many years. Long noncoding RNAs (lncRNAs) are emerging as new regulators of diverse cellular process; however, little is known about the role of lncRNAs in the cellular response to UV treatment. Here, we demonstrate that levels of lncRNA-HOTTIP significantly increases after UV stimulation and regulates the UV-mediated cellular response to UV through the coordinate activation of its neighboring gene Hoxa13 in GC-1 cells (spermatogonia germ cell line). UV-induced, G2/M-phase arrest and early apoptosis can be regulated by lncRNA-HOTTIP and Hoxa13. Furthermore, lncRNA-HOTTIP can up-regulate ${\gamma}-H_2AX$ and p53 expression via Hoxa13 in UV-irradiated GC-1 cells. In addition, p53 has the ability to regulate the expression of both lncRNA-HOTTIP and Hoxa13 in vitro and in vivo. Our results provide new data regarding the role lncRNAs play in the UV response in spermatogenic cells.

• Molecular & Cellular Toxicology
• /
• 제1권2호
• /
• pp.73-77
• /
• 2005

Nickel is the one of potent environmental, the occupational pollutants and the classified human carcinogens. It is a serious hazard to human health, when the metal exposure. To prevent human diseases from the heavy metals, it is seemingly important that understanding of how nickel exerts their toxicity and carcinogenic effect at a molecular and a genomic level. The process of nickel absorption has been demonstrated as phagocytosis, iron channel and diffusion. Uptaked nickel has been suggested to induce carcinogenesis via two pathways, a direct DNA damaging pathway and an indirect DNA damaging pathway. The former was originated from the ability of metal to generate Reactive Oxygen Species (ROS) and the reactive intermediates to interact with DNA directly. Ni-generated ROS or Nickel itself, interacts with DNAs and histones to cause DNA damage and chromosomal abnormality. The latter was originated from an indirect DNA damage via inhibition of DNA repair, or condensation and methylation of DNA. Cells have ability to protect from the genotoxic stresses by changing gene expression. Microarray analysis of the cells treated with nickel or nickel compounds, show the specific altered gene expression profile. For example, HIF-I (Hypoxia-Inducible Factor I) and p53 were well known as transcription factors, which are upregulated in response to stress and activated by both soluble and insoluble nickel compounds. The induction of these important transcription factors exert potent selective pressure and leading to cell transformation. Genes of metallothionein and family of heat shock proteins which have been known to play role in protection and damage control, were also induced by nickel treatment. These gene expressions may give us a clue to understand of the carcinogenesis mechanism of nickel. Further discussions on molecular and genomic, are need in order to understand the specific mechanism of nickel toxicity and carcinogenicity.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권9호
• /
• pp.4199-4204
• /
• 2016

Cancer is a complex disease caused by a progressive accumulation of multiple genetic mutations. Consumption of fruits is associated with lower risk of several cancers, which is mainly associated to their phytochemical content. The use of functional foods and chemopreventive compounds seems to contribute in this process, acting by mechanisms of antioxidant, anti-inflammatory, anti-angiogenic and hormonal. The Psidium Guajava has high potential functional related to pigments who are involved in the process of cancer prevention by having antioxidant activity. The aim of the present review is to expose some chemical compounds from P. Guajava fractions and their association with anti-carcinogenic function. The evidences supports the theory of anticancer properties of P. Guajava, although the mechanisms are still not fully elucidated, but may include scavenging free radicals, regulation of gene expression, modulation of cellular signalling pathways including those involved in DNA damage repair, cell proliferation and apoptosis.

• 대한의생명과학회지
• /
• 제22권1호
• /
• pp.18-23
• /
• 2016

Ultraviolet (UV) irradiation induces cellular damage. A variety of cellular responses for repairing cellular damage including DNA damage occur after UV irradiation. During the repair processes, expression and activation of various molecules are regulated depending on the types of cellular damage. Parkin is an E3 ligase and act as a tumor suppressor. Recently, it has been reported that Parkin is involved in the DNA repair process. In the current study, we investigated whether UVB irradiation influences expression of Parkin. Parkin expression transiently decreased after UVB irradiation both at the mRNA and protein levels, but returned to normal levels thereafter. Taken together with cell viability data, Parkin expression is down-regulated during UVB-induced suppression of cell growth and is increased again in accordance with recovery of UVB-induced cell growth inhibition. However, Parkin overexpression or knockdown did not influence UVB-induced cell growth inhibition and recovery. We propose that Parkin could be a useful molecular marker for evaluating conditions of cells after UVB irradiation.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권5호
• /
• pp.2273-2278
• /
• 2014

Purpose: The purpose of our study was to explore the molecular mechanisms in the process of oral squamous cells carcinoma (OSCC) development. Method: We downloaded the affymetrix microarray data GSE31853 and identified differentially expressed genes (DEGs) between OSCC and normal tissues. Then Gene Ontology (GO) and Protein-Protein interaction (PPI) networks analysis was conducted to investigate the DEGs at the function level. Results: A total 372 DEGs with logFCI >1 and P value < 0.05 were obtained, including NNMT, BAX, MMP9 and VEGF. The enriched GO terms mainly were associated with the nucleoplasm, response to DNA damage stimuli and DNA repair. PPI network analysis indicated that GMNN and TSPO were significant hub proteins and steroid biosynthesis and synthesis and degradation of ketone bodies were significantly dysregulated pathways. Conclusion: It is concluded that the genes and pathways identified in our work may play critical roles in OSCC development. Our data provides a comprehensive perspective to understand mechanisms underlying OSCC and the significant genes (proteins) and pathways may be targets for therapy in the future.

• Clinical and Experimental Pediatrics
• /
• 제48권12호
• /
• pp.1295-1309
• /
• 2005

Nowadays, the nutritional deficits are rarely seen in Korea. However, an increased availability of the highly palatable energy dense, nutrient-poor foods increases the risks of obesity and deficits of vitamins and minerals in the general population. Also, optimum intake of vitamins and minerals, which varies with age and genetic back ground, might not suffice the poor, young, obese, and elderly people. Young girls and individuals participating in weight reductions and aesthetic components are prone to micronutrient deficiencies because they restrict food intake and specific micronutrient rich foods. An inadequate intake of vitamins or minerals is associated with reduced physical performance and exercise capacity, increased obesity, decreased cognitive function, increased DNA damages such as single- and double-stranded breaks or oxidative DNA lesions, and accelerated aging process and increased neuronal damages with mitochondrial oxidative decay. Most of these deleterious effects of the deficit could be prevented by a one tablet of multivitamins with a good balanced diet. High dose B vitamins are frequently administered to overcome the metabolic inadequacy to the people with the less functional enzymes with increased Km values for their coenzymes due to the single gene mutation or due to the single nucleotide polymorphisms. And some certain antioxidant vitamins are also used in large quantities to overcome the oxidative stress and to repair the damages. In this review, new nutritional concepts of some vitamins and minerals, which are widely used and useful for the children, will be discussed.