• Environmental Analysis Health and Toxicology
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• v.19 no.4
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• pp.335-344
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• 2004

Diesel exhaust particle (<2.5 ${\mu}{\textrm}{m}$, DEP$_{2.5}$) is known to be probarbly carcinogenic (IARC group 2A). DEP$_{2.5}$ contains organic compounds such as polycyclicaromatic hydrocarbon (PAH), heterocyclic compounds, phenols, and nitroarenes. Reactive oxygen species (ROS) are generated by DEP$_{2.5}$ without any biological activation system. Therefore, an alternative mechanism by which DEP$_{2.5}$ could be carcinogenic is known by the generation of oxidative DNA damage. The aim of this study was to investigate genotoxic effects of DEP$_{2.5}$ using single cell gel electrophoresis. In order to evaluate the mechanisms of DEP$_{2.5}$ genotoxicity, the rat micro-some mediated and DNA repair enzyme treated comet assays together with routine comet assay were performed. DEP$_{2.5}$ was collected from diesel engine bus and dichloromethane extract was obtained. The organic extract of DEP$_{2.5}$ revealed DNA damage itself in NIH/3T3 cells. And it showed both oxidative and microsome mediated DNA damages. Vitamin C as an model antioxidant reduced DNA damage in endonuclase III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor reduced DNA damage in the presence of S-9 mixture. Our results show that DEP$_{2.5}$ are genotoxic and a great source of oxidative stress, but antioxidants can significantly reduce oxidative DNA damages. And DEP$_{2.5}$ may contain indirect mutagens which can be inhibited by CYP inhibitors.d by CYP inhibitors.

• Molecules and Cells
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• v.20 no.2
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• pp.228-234
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• 2005

Caenorhabditis elegans him-6 mutants, which show a high incidence of males and partial embryonic lethality, are defective in the orthologue of human Bloom's syndrome protein (BLM). When strain him-6(e1104) containing a missense him-6 mutation was irradiated with ${\gamma}$-rays during germ cell development or embryogenesis, embryonic lethality was higher than in the wild type, suggesting a critical function of the wild type gene in mitotic and pachytene stage germ cells as well as in early embryos. Even in the absence of ${\gamma}$-irradiation, apoptosis was elevated in the germ cells of the him-6 strain and this increase was dependent on a functional p53 homologue (CEP-1), suggesting that spontaneous DNA damage accumulates due to him-6 deficiency. However, induction of germline apoptosis by ionizing radiation was not significantly affected by the deficiency, indicating that HIM-6 has no role in the induction of apoptosis by exogenous DNA damage. We conclude that the C. elegans BLM orthologue is involved in DNA repair in promeiotic cells undergoing homologous recombination, as well as in actively dividing germline and somatic cells.

• Animal cells and systems
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• v.16 no.3
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• pp.173-182
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• 2012

The p53 protein plays a pivotal role in tumor suppression. The cellular level of p53 is normally kept low by proteasome-mediated degradation, allowing cell cycle progression and cell proliferation. Under stress conditions, such as DNA damage, p53 is stabilized and activated through various post-translational modifications of itself as well as of its regulatory proteins for induction of the downstream genes responsible for cell cycle arrest, DNA repair, and apoptosis. Therefore, the level of p53 should be tightly regulated for normal cell growth and for prevention of the accumulation of mutations in DNA under stress conditions, which otherwise would lead to tumorigenesis. Since the discovery of Mdm2, a critical ubiquitin E3 ligase that destabilizes p53 in mammalian cells, nearly 20 different E3 ligases have been identified and shown to function in the control of stability, nuclear export, translocation to chromatin or nuclear foci, and oligomerization of p53. So far, a large number of excellent reviews have been published on the control of p53 function in various aspects. Therefore, this review will focus only on mammalian ubiquitin E3 ligases that mediate proteasome-dependent degradation of p53.

• Journal of Radiation Protection and Research
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• v.34 no.1
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• pp.15-24
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• 2009

The effect of low doses of ultraviolet (UV) irradiation on morphology changes of cell has been studied based on the observation of the cell length. It was shown that UV-irradiated cell has different behavior in comparison with non-irradiated cell. From the histogram of cell-length distribution, it was confirmed that cell cycle of non irradiated cell was 28 hours, and that cell cycle of irradiated cell with dose of $20\;Jm^{-2}$ was delayed (39 hours), while irradiated cell with $40\;Jm^{-2}$ and $60\;Jm^{-2}$ did not divide and kept growing continuously. It was supposed that in case of $20\;Jm^{-2}$ of irradiation dose, the cell cycle was delayed because the checkpoint worked in order to repair DNA damage induced by generation of pyrimidine dimer, reactive oxygen species and so on. It was also supposed that in case of $40\;Jm^{-2}$ and $60\;Jm^{-2}$ of irradiation dose, overgrowth was induced because the checkpoint was not worked well. The morphology of overgrown cell was similar to that of normally senescent cell. Therefore, it was considered that cell senescence was accelerated by UV irradiation with irradiation doses of $40\;Jm^{-2}$ and $60\;Jm^{-2}$.

• Journal of Life Science
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• v.13 no.3
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• pp.241-247
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• 2003

While the DNA-protein kinase (DNA-PK) complex, comprised of DNA-PKcs and Ku80, is primary involved in the repair of DNA double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts (MEFs) derived from either wild-type (Wt) or DNA-PKcs-null (DNA-$PKcs^{-/-}$) mice with various stress inducing agents revealed that adriamycin was markedly more cytotoxic for $Ku80^{-/-}MEFs$ and led to their long-term accumulation in the $G_2$/M phase. This differential response was not due to differences in DNA repair, since adrimycin-triggered DNA damage was repaired with comparable efficiency in both Wt and $Ku80^{-/-}MEFs$, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and $G_2$/M-progression are not only dependent on the cell's DNA repair but also may reflect Ku80's influence on additional cellular processes such as gene expression.

• The Journal of Korean Medicine
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• v.33 no.3
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• pp.133-146
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• 2012

Background: Most antitumor agents have the side effect of chemotherapy-induced peripheral neuropathy (CIPN). Cancer patients who take antitumor agents suffer from CIPN, but there is no known treatment for it. Unlike the central nerve system, the peripheral nerve can self-repair, and the Schwann cell takes this mechanism. Objectives: In this study, we researched the effect of YideungJetong-Tang (YJT) extract on taxol-induced sciatic nerve damage, through in vitro and in vivo experiments. Also, we studied the effect of YJT extract on neurite recovery and anti-inflammatory effect after compression injury of sciatic nerve in vivo. Methods: Vehicle, taxol and taxol+YJT were respectively applied on sciatic nerve cells of rat in vitro, then the cells were cultured. The sciatic nerve cells and Schwann cells were then observed using Neurofilament 200, Hoechst, ${\beta}$ -tubulin, S-$100{\beta}$, caspase-3 and phospho-Erk1/2. CIPN was induced by taxol into the sciatic nerve of rat in vivo, then YJT extract was taken orally. The axons, Schwann cells and neurites of the DRG sensory nerve were then observed using Neurofilament 200, ${\beta}$-tubulin, Hoechst, S-$100{\beta}$, phospho-Erk1/2 and caspase-3. YJT was taken orally after sciatic nerve compression injury, and the changes in axon of the sciatic nerve, Schwann cells and TNF-${\alpha}$ concentration were observed. Results: The taxol and YJT treated group showed significant effects on Schwann cell recovery, neurite growth and recovery. In vivo, YJT compared with control group showed Schwann cell structural improvement and axons recovering effect after taxol-induced Schwann cell damage. After sciatic nerve compression injury, recovery of distal axon, changes of Schwann cell distribution, and anti-inflammatory response were observed in the YJT. Conclusions: Through this study, we found that after taxol-induced neurite damage of sciatic nerve in vivo and in vitro, YJT had significant effects on sciatic nerve growth and Schwann cell structural improvement. In vivo, YJT improved recovery of distal axons and Schwann cells and had an anti-inflammatory effect.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.138-150
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• 2004

Objectives : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions, including Sesim-tang, have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. The present study investigated the effects of Sesim-tang on apoptotic cell death induced by CT105 (carboxy terminal 105 amino acid peptide fragment of APP) overexpression in SK-N-SH neuroblastoma cell lines. Methods: We studied the regenerative and inhibitory effects on Alzheimer's disease in CT105-induced SK-N-SH cell lines by Sesim-tang water extract. We examined for cell morphological pattern, DNA fragmentation, LDH activity assay, zymography assay, and immunohistochemistric analysis. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. Results: Findings from our experiments have shown that Sesim-tang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in the cell line. In addition, pretreatment with Sesim-tang ($>50\mu\textrm{g}/ml$ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines. SK-N-SH cell lines overexpressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase-contrast microscope and LDH activity measurements in the culture media, the CT105-induced cell death was significantly inhibited by Sesim-tang water extract. Sesim-tang was found to reduce the expression of APP and caspase-3 induced by CT105 in SK-N-SH cell lines and in rat hippocampus. Conclusions: As the result of this study, in the Sesim-tang group, apoptosis in the nervous system is inhibited, the repair against the degeneration of SK-N-SH cell lines by CT105 expression is promoted. Hence, Sesim-tang may be beneficial for the treatment of AD.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.170-178
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• 2022

The airway epithelium is equipped with the ability to resist respiratory disease development and airway damage, including the migration of airway epithelial cells and the activation of TLR3, which recognizes double-stranded (ds) RNA. Primary cilia on airway epithelial cells are involved in the cell cycle and cell differentiation and repair. In this study, we used Beas-2B human bronchial epithelial cells to investigate the effects of the TLR3 agonist polyinosinic:polycytidylic acid [Poly(I:C)] on airway cell migration and primary cilia (PC) formation. PC formation increased in cells incubated under serum deprivation. Migration was faster in Beas-2B cells pretreated with Poly(I:C) than in control cells, as judged by a wound healing assay, single-cell path tracking, and a Transwell migration assay. No changes in cell migration were observed when the cells were incubated in conditioned medium from Poly(I:C)-treated cells. PC formation was enhanced by Poly(I:C) treatment, but was reduced when the cells were exposed to the ciliogenesis inhibitor ciliobrevin A (CilioA). The inhibition of Beas-2B cell migration by CilioA was also assessed and a slight decrease in ciliogenesis was detected in SARS-CoV-2 spike protein (SP)-treated Beas-2B cells overexpressing ACE2 compared to control cells. Cell migration was decreased by SP but restored by Poly(I:C) treatment. Taken together, our results demonstrate that impaired migration by SP-treated cells can be attenuated by Poly(I:C) treatment, thus increasing airway cell migration through the regulation of ciliogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.9-21
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• 2015

Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancer-related mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.

• Journal of Life Science
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• v.16 no.4
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• pp.704-709
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• 2006

The present study intends to characterize the DNA damage-inducible responses in Caenorhabditis elegans. To study UV-inducible responses in C. elegans, two UV-inducible cDNA clones were isolated from C. elegans by using subtration hybridization method. To investigate the expression of isolated genes, UV100 and UV150, the cellular levels of the transcript were determined by Northern blot analysis after UV-irradiation. The transcripts of isolated gene increased rapidly and reached maximum accumulation after UV-irradiation. Compared to the message levels of control, the levels of maximal increase were approximately 2 folds to UV-irradiation. These results implied that the effects of damaging agents are complex and different regulatory pathways exist for the induction of these genes. To study the function of UV100 and UV150 gene in response to UV irradiation, we carried out a RNAi experiment and investigated the UV sensivity. This result indicated that UV100 gene involved in stage-specific repair pathway or regulated by development.