• Title/Summary/Keyword: High throughput screen

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Proteome in Toxicological Assessment of Endocrine Disrupting Chemicals (프로테오믹스를 이용한 내분비계 교란물질 환경독성 연구)

  • 김호승;계명찬
    • Korean Journal of Environmental Biology
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    • v.21 no.2
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    • pp.87-100
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    • 2003
  • It is important to understand the potential human health implications of exposure to environmental chemicals that may act as hormonally active agents. It is necessary to have an understanding of how pharmaceutical and personal care products and other chemicals affect the ecosystem of our planet as well as human health. Endocrine disruption is defined as the ability of a chemical contaminating the workplace or the environment to interfere with homeostasis, development, reproduction, and/or behavior in a living organism or it's offspring. Certain classes of environmentally persistent chemicals such as polychlorinated biphenyls (PCBs), dioxins, furans, and some pesticides can adversely effect the endocrine systems of aquatic life and terrestrial wildlife. Research continues to support the theory of endocrine disruption. However, endocrine disruption researches have been applied to proteomics poorly. Proteomics can be defined as the systematic analysis of proteins for their identity, quantity and function. It could increase the predictability of early drug development and identify non-invasive biomarkers of tonicity or efficacy. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis (2D/E) and MALDI-TOF mass spectrometry (MS) sr protein chip array and SELDI-TOF MS. Proteomics have an opportunity to play an important role in resolving the question of what role endocrine disruptors play in initiating human disease. Proteomics can also play an imfortant role in the evaluation of the risk assessment and use of risk management and risk communication tools required to address public health concerns related to notions of endocrine disruptors. Understanding the need for the proteomics and possessing knowledge of the developing biomakers used to abbess endocrine activity potential will he essential components relevant to the topic of endocrine disruptors.

GENE EXPRESSION PATTERNS INDUCED BY $TAXOL^{(R)}$ AND CYCLOSPORIN A IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE USING CDNA MICROARRAY (cDNA Microarray를 이용한 구강편평세포암종 세포주에서 $Taxol^{(R)}$과 Cyclosporin A로 유도된 유전자 발현양상)

  • Kim, Yong-Kwan;Lee, Jae-Hoon;Kim, Chul-Hwan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.3
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    • pp.202-212
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    • 2006
  • It is well-known that paclitaxel($Taxol^{(R)}$), which is extracted from the pacific and English yew, has been used as a chemotherapeutic agent for ovarian carcinoma and advanced breast carcinoma and Cyclosporin A, which is highly lipophilic cyclic peptide and isolated from a fungus, has been also used as an useful immunosuppressive drug after transplantation and is associated with cellular apoptosis. Since 1953, in which James Watson, Rosalind Franklin and Francis Crick discovered the double helical structure of DNA, a few kinds of techniques for identifying gene expression have been developed. In postgenomic period, many of researchers have used the DNA microarray which is high throughput screening technique to screen large numbers of gene expression simultaneously. In this study, we searched and screened the gene expression in the oral squamous cell carcinoma cell lines treated with $Taxol^{(R)}$, cyclosporin or cyclosporin combined with $Taxol^{(R)}$ using cDNA microarray. The results were as following; 1. It was useful that the appropriate concentration of Cyclosporin A and $Taxol^{(R)}$ used in oral squamous cell carcinoma cell line was under 1${\mu}g/ml$ and 3${\mu}g/ml$. 2. In the experimental group in which $Taxol^{(R)}$ and $Taxol^{(R)}$ + Cyclosporin A were used, the cell growth was extremely decreased. 3. In the group in which Cyclosporin A was used, the MTT assay was rarely decreased which means the activity of succinyl dehydrogenase is remained in mitochondria but in the group in which the mixture of Cyclosporin A and $Taxol^{(R)}$ were used, the MTT assay was extremely decreased. 4. In the each group in which Cyclosporin A(3 ${\mu}g/ml$) and $Taxol^{(R)}$(1 ${\mu}g/ml$) were used, the cell arrest was appeared in $G_2/M$ phase and in the group in which $Taxol^{(R)}$(3 ${\mu}g/ml$) was used, the cell arrest was appeared in both S phase and $G_2/M$ phase. 5. In the oral squamous cell carcinoma cell line treated with $Taxol^{(R)}$, several genes including ANGPTL4, RALBP1 and TXNRD1, associated with apoptosis, SUI1, MAC30, RRAGA and CTGF, related with cell growth, HUS1 and DUSP5, related with cell cycle and proliferation, ATF4 and CEBPG, associated with transcription factor, BTG1 and VEGF, associated with angiogenesis, FDPS, FCER1G, GPA33 and EPHA4 associated with signal transduction and receptor activity and AKR1C2 and UGTA10 related with carcinogenesis were detected in increased levels. The genes that showed increaced expression in the oral squamous cell carcinoma cell line treated with Cyclosporin A were CYR61, SERPINB2, SSR3 and UPA3A which are known as genes associated with cell growth, carcinogenesis, receptor activity and transcription factor. The genes expressed in the HN22 cell line treated with cyclosporin combined with $taxol^{(R)}$ were ALCAM and GTSE1 associated with cancer invasiveness and cell cycle regulation.