• Toxicological Research
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• v.20 no.1
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• pp.71-82
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• 2004

Changes in cell cycle control in the lungs and liver of the B6C3F1 mice (20 males per each group) exposed to ozone (0.5 ppm), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1.0 mg/kg), and dibutyl phthalate (DBP, 5,000 ppm) after 52 weeks were examined through Western, Northern blot, and immunohistochemistry based on alterations in protein expression levels of G1/S checkpoints (cyclin D1, cyclin E, and PCNA), G2/M checkpoints (cyclin B1, cyclin G, and cyclin A), negative regulators (p53, p21, GADD45, and p27), and positive regulator (mdm2). Expression levels of cyclins D1, E, G, PCNA, mutant p53, and mdm2 proteins were higher in the lungs and livers treated with combination of toxicants than in those treated with ozone only. Expression levels of the wild-type and mutant p53, p21, GADD45, p27, and mdm2 proteins and mRNAs were higher in toxicant-treated groups than those of the control. Immunohistochemical analysis revealed staining intensities of the PCNA, cyclin D1, c-myc and mdm2 protein- treated lungs and livers were stronger than those of the control group. Our results showed that combined treatment of ozone with NNK/DBP altered the cell cycle control through instability of the wild-type p53 gene. Such pivotal p53-mediated cell cycle alterations may be responsible for the toxicity observed under our experimental condition. These results may be applied to risk assessment of mixture-induced toxicity.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.246-252
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• 2002

Purpose : It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. Materials and Method : Mice with mutations in Fas, $MRL/Mpj-Fas^{Ipr}$, and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, $Bcl-X_L,\;and\;Bcl-X_S$ were also analyzed by Western blotting. Results : At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in $MRL/Mpj-Fas^{Ipr}$. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and $MRL/Mpj-Fas^{Ipr}$ mice were $52.3{\pm}7.8\%\;and\;8.0{\pm}8.6\%$, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, $Bcl-X_L\;and\;Bcl-X_S$, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, $Bcl-X_L$ with a peak level of 3.3-fold at 12 h, and $Bcl-X_S$ with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in $MRL/Mpj-Fas^{Ipr}$ mice, the expression levels of p53, Bcl-2, Bax, $BCl-X_L\;and\;BCl-X_S$ showed no significant change. Conclusion : The level of radiation-induced apoptosis was lower in Fas mutated mice, Ipr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the Ipr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5663-5667
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• 2015

Background: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancer risk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis to investigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in Saudi Arabia. Materials and Methods: We searched all eligible published studies and data were pooled together to perform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for homozygous, heterozygous, dominant and recessive genetic models. Results: A total of five eligible published studies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publication bias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95% CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous (Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancer risk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive (Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increased risk of cancer. Conclusions: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism of the p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large case control studies are needed to validate our findings.

• Animal cells and systems
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• v.11 no.1
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• pp.9-15
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• 2007

The naphthoquinone analog (2,3-dichloro-6,9-dihydroxy-1,4-naphtoquinone, NA) has an inhibitory effect on cdc25A protein phosphatase in vitro, which is responsible for G1/S transition during cell cycle. However, the exact mechanism inducing the growth inhibition is not understood. In this study, we investigated the regulatory mechanisms of growth arrest induced by NA, as a new potent inhibitor of cdc25A phosphatase, in human hepatocarcinoma SK-hep-1 cells. We found that NA induced the G1 arrest by perturbation of protein tyrosine dephosphorylation of Cdk2, which may be resulting from inhibition of cdc25A phosphatase. In addition, p21 was expressed in a p53-independent manner and participated in the NA-induced G1 arrest by inhibiting Cdk2 activity. Although the exact mechanism is not known, the p21 expression might be related to MAPK activation. From these results, we suggest that NA induces G1 arrest via inhibition of cdc25A and induction of p53-independent p21 expression in SK-Hep-1 cells.

• 대한예방의학회:학술대회논문집
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• 1999.10a
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• pp.138-139
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• 1999

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.38.1-38.1
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• 2008

• Kyungpook Mathematical Journal
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• v.53 no.4
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• pp.615-624
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• 2013

The object of the present paper is to investigate the majorization properties of certain subclasses of analytic p-valent functions defined by convolution.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.107-107
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• 2004

• Proceedings of the Korean Biophysical Society Conference
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• 2001.06a
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• pp.59-59
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• 2001

The purpose of this study was to investigate the molecular mechanism by which environmental pH alters the radiation-induced expression of p53, the key regulator of cellular responses to radiation. We have already reported that an acidic environment markedly prolongs the radiation-induced expression of p53 and also prolongs the radiation-induced G2/M arrest.(omitted)

• Journal of Life Science
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• v.22 no.3
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• pp.360-365
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• 2012

We investigated the anti-proliferative activity of sulforaphane and expression changes of NAG-1 and p21 genes in response to sulforaphane treatment in human colorectal HCT116 cells. The results showed that sulforaphane decreased cell viabilities in a dose-dependent manner and induced expression of NAG-1 and p21 proteins in a dose-dependent and time-dependent manner. In addition, we found that NAG-1 expression by sulforaphane was not dependent on the presence of p53, whereas p21 expression was dependent on p53 presence. The results indicated that up-regulation of NAG-1 was not related with the activity of a dietary histone deacetylase inhibitor of sulforaphane. ATF3 induction was detected from 2 hr after sulforaphane treatment, indicating that ATF3 could be a transcription factor to up-regulate NAG-1 expression. The results of this study may help to increase our understanding of the molecular mechanism of anti-cancer activity mediated by sulforaphane in human colorectal cancer cells.