• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.84-84
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• 2002

Abstract To study the status of oxidative DNA damage in Helicobacter pylori infection in more details, gene-specific oxidative DNA damage was investigated by examining oxidative DNA damage to individual genes. This was done by determining the loss of PCR product of a targeted gene before and after gastric mucosal DNA was treated with 8-hydroxyguanine glycosylase, which cleaves DNA at the 8-hydroxyguanine residues.(omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.84-84
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• 2002

• International Journal of Oral Biology
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• v.47 no.2
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• pp.17-24
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• 2022

Preserving intact genetic material and delivering it to the next generation are the most significant tasks of living organisms. The integrity of DNA sequences is under constant threat from endogenous and exogenous factors. The accumulation of damaged or incompletely-repaired DNA can cause serious problems in cells, including cell death or cancer development. Various DNA damage detection systems and repair mechanisms have evolved at the cellular level. Although the mechanisms of these responses have been extensively studied, the global RNA expression profiles associated with genomic instability are not well-known. To detect global gene expression changes under different DNA damage and hypoxic conditions, we performed RNA-seq after treating human cervical cancer cells with ionizing radiation (IR), hydroxyurea, mitomycin C (MMC), or 1% O₂ (hypoxia). Results showed that the expression of 184-1037 genes was altered by each stimulus. We found that the expression of 51 genes changed under IR, MMC, and hypoxia. These findings revealed damage-specific genes that varied differently according to each stimulus and common genes that are universally altered in genetic instability.

• BMB Reports
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• v.32 no.6
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• pp.554-560
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• 1999

TTD1BI cells are non-hypersensitive to UV irradiation and perform normal genome repair of pyrimidine dimers but fail to excise 6-4 photoproducts and, concomitantly, are unable to restore RNA synthesis levels following UV irradiation. This pointed to a detect in gene-specific repair and this study was undertaken to examine repair of 6-4 photoproducts at the gene-level. The results indicated a defect in gene-specific repair of 6-4 photoproducts in active genes, although strand-specificity of 6-4 photoproduct removal was essentially similar to that of normal cells. These findings indicate that the near normal UV resistance of TTD1BI cells may be due to the inability of these cells to remove DNA lesions preferentially, as well as to the cells opting out of the cell cycle to repair damage before resuming replication.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.26-26
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• 2001

8-Hydroxyguanine(oh$\^$8/Gua), an oxidative DNA adduct is a most easily and abundantly formed base modification. What we have known about oh$\^$8/Gua so far is that this DNA adduct mediates the mutagenesis and it is used as a useful marker of oxidative DNA damage. We found additional evidence and here present them: 1) oh$\^$8/Gua in DNA can trigger cell death by inducing cell cycle arrest and apoptosis and 2) it can be used to assess the oxidative damage of each individual gene.(omitted)

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.73-77
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• 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.

• Animal cells and systems
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• v.6 no.3
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• pp.263-269
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• 2002

The p53 tumor suppressor gene is among the most frequently mutated and studied genes in human cancer, but the mechanisms by which it sur presses tumor formation remain unclear. DNA damage regulates both the protein levels of p53 and its affinity for specific DNA sequences. Stabilization of p53 in response to DNA damage is caused by its dissociation from Mdm2, a downstream target gene of p53 and a protein that targets p53 for degradation in the proteosome. Recent studies have suggested that phosphorylation of human p53 at Ser20 is important for stabilizing p53 in response to DNA damage through disruption of the interaction between Mdm2 and p53. We generated mice with an allele encoding changes at Ser20, known to be essential for p53 accumulation following DNA damage, to enable analyses of p53 stabilization in vivo. Our data showed that the mutant p53 was clearly defective for full stabilization of p53 in response to DNA damage. We concluded that Ser20 phosphorylation is critical for modulating the negative regulation of p53 by Mdm2, probably through phosphorylation-dependent inhibition of p53-Mdm2 interaction in the physiological context.

• Animal cells and systems
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• v.6 no.4
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• pp.311-315
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• 2002

The RAD4 gene is essential for nucleotide excision repair in Saccharomyces cerevisiae. It has been known that the deduced amino acid sequence of Rad4 protein contains three DNA-dependent ATPase/helicase motifs. To determine the biochemical activities and functional role of RAD4 the Rad4 protein was expressed and purified. Immunoblot analysis showed a specific band of 21 kDa, which was well-matched with the size of open reading frame of the RAD4 gene. The purified Rad4 protein had no detectable helicase activity. However, the protein could interact with double stranded oligonucleotides, as judged by mobility shift assay. This result suggests that the Rad4 protein is a DNA binding protein.

• Korean Journal of Environmental Biology
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• v.23 no.1
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• pp.21-26
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• 2005

Cell response to genotoxic agents is complex and involves the participation of different classes of genes including cell cycle control, DNA repair and apoptosis. In this report, we presented a approach to characterize the cellular functions associated with the altered transcript profiles of MCF-7 exposed to low-dose in vitro gamma-irradiation. We used the method of human 2.4 k cDNA microarrays containing apoptosis, cell cycle, chromatin, repair, stress and chromosome genes to analyze the differential gene expression characterization that were displayed by radiation-exposed cell, human breast carcinoma MCF-7 cell line, such as 4 Gy 4 hr, 8 Gy 4 hr, and 8 Gy 12 hr. Among these genes, 66 were up-regulated and 49 were down-regulated. Specific genes were concomitantly induced in the results. Cyclin dependent kinase 4 (Cdk4) is induced for starting the cell cycle. This regulation is required for a DNA damage­induced G1 arrest. In addition to, an apoptotic pathways gene Bcl-w was concomitantly induced. Mismatch repair protein homologue-l (hMLH1), a necessary component of DNA mismatch protein repair (MMR), in G2-M cell cycle checkpoint arrest. The present study provides new information on the molecular mechanism underlying the cell response to genotoxic stress, with relevance to basic and clinical research.

• Journal of Genetic Medicine
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• v.2 no.1
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• pp.31-34
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• 1998

The N-methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, removes N-methylpurine and other damaged purines induced in DNA. Tissue-specific mRNA levels of the N-methylpurine-DNA glycosylase (MPG) were investigated in Balb/c mice of four different growing stages; newborn, 1, 4 and 8-weeks postpartum. MPG expressions in the newborn and the 8-week-old mice were the highest in thymus and testis, respectively. The tested tissues of the newborn mice had consistently higher MPG mRNA level than 8-week-old adults except in testis and thymus. The MPG mRNA level in testis was the lowest in the newborn mice, but it attained the highest in the 8-week-old mice. The levels of MPG mRNA among the different tissues in the newborn and the 8-week-old mice were more than 9.0 and 19.0-fold respectively. These results suggest that the of MPG expression was dependent on the growing stage and had tissue-specificity.