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Lee, Mi-Ni,Lee, Shi-Nai,Kim, Se-Hee,Kim, Bora,Jung, Bo-Kyung,Seo, Ji Hae,Park, Ji-Hyeon,Choi, Jae-Hoon,Yim, Sun Hee,Lee, Mi-Ran,Park, Jong-Gil,Yoo, Ji-Young,Kim, Jeong Hun,Lee, Seung-Taek,Kim, Hwan-Mo Oxford University Press 2010 Journal of the National Cancer Institute Vol.102 No.6
<P><B>Background</B></P><P>Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A<SUP>225</SUP>) acetylates HIF-1α, triggering its degradation, and thus may play a role in decreased expression of VEGFA.</P><P><B>Methods</B></P><P>We generated Apc<SUP>Min/+</SUP>/mARD1A<SUP>225</SUP> transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A<SUP>225</SUP> were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A<SUP>225</SUP> acetylation of Lys532 in HIF-1α, we injected B16F10-mARD1A<SUP>225</SUP> cell lines stably expressing mutant HIF-1α/K532R into mice and measured metastasis. All statistical tests were two-sided, and <I>P</I> values less than .05 were considered statistically significant.</P><P><B>Results</B></P><P>Apc<SUP>Min/+</SUP>/mARD1A<SUP>225</SUP> transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than Apc<SUP>Min/+</SUP> mice (n = 21) (number of intestinal polyps per mouse: Apc<SUP>Min/+</SUP> mice vs Apc<SUP>Min/+</SUP>/mARD1A<SUP>225</SUP> transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; <I>P</I> < .001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A<SUP>225</SUP>-overexpressing cells than in mice injected with control cells (<I>P</I> < .01). Moreover, overexpression of mARD1A<SUP>225</SUP> decreased VEGFA expression and microvessel density in tumor xenografts (<I>P</I> < .04) and Apc<SUP>Min/+</SUP> intestinal polyps (<I>P</I> = .001). Mutation of lysine 532 of HIF-1α in B16F10-mARD1A<SUP>225</SUP> cells prevented HIF-1α degradation and inhibited the antimetastatic effect of mARD1A<SUP>225</SUP> (<I>P</I> < .001).</P><P><B>Conclusion</B></P><P>mARD1A<SUP>225</SUP> may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis.</P>
모작업장에서 휘발성 유기오염물질의 분석과 근로자들의 건강위해성 평가
이효민,김명수,최시내,윤은경,박종세,Lee, Hyo-Min,Kim, Myung-Soo,Choi, Shi-Nai,Yoon, Eun-Kyung,Park, Jong-Sei 대한예방의학회 1997 예방의학회지 Vol.30 No.3
This study was conducted to assess the health risk on the volatile organic compounds such as toluene, xylene, and styrene in painting workplace. It was monitored through personal air sampling during working time in selected 5 workplaces and analysed using gas chromatography. For the settlement of exposure situation, there were regarded working conditions such as working hours, yearly working days, and working years. Also, Monte-Carlo simulation was used for the induction of hazard index using toxicity value from IRIS(Integrated risk information system) database. The results of risk assessment were summarized as follows. 1. The air concentration of toluene was $7.096{\pm}15,644ppm,\;2.586{\pm}4.275ppm\;for\;xylene,\;1.914{\pm}5.320ppm$ for styrene in blast painting workplaces. The level of toluene was different significantly compared with the level of xylene and styrene. 2. Computated chronic daily intake values of 95th percentile on toluene, xylene and styrene treated by Monte-Carlo simulation were 9.616, 3.567, 2.782 mg/kg/day, respectively. 3. Computated hazard index values of 75th percentile on toluene, xylene and styrene treated by Monte-Carlo simulation were 3.5, 1.0 and 1.6, respectively. Adverse health effects on the toluene, xylene and styrene would be expected by working exposure in selected 5 workplaces since the hazard indices of three compounds were exceeded 1 in the surroundings of 75th percentile though having the low emerged frequency.