Development of evaluation system for cancer chemopreventive agents based on DNA damage inhibition and gene expression
基于DNA损伤抑制和基因表达的癌症化学预防剂评价体系的开发
基本信息
- 批准号:13557030
- 负责人:
- 金额:$ 9.09万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2003
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Antioxidantg, such as vitamins and flavonoids contained in vegetables and fruits, have been believed to play the key role in cancer prevention. However, epidemiological studies demonstrated that b-carotene increased the incidences of lung cancer. We reported that b-carotene metabolites induced oxidative DNA damage. To establish the method to promote effective and Safe cancer chemoprevention, we investigated DNA damage and gene expression induced by chemopreventive agents as follows1. Phytic acid contained in cereals inhibited oxidative DNA damage in cultured cells. Phytic acid alone did not cause DNA damage. Thus, it can be a promising cancer chemopreventive agent.2. Although curcumin exhibits antitumor activity, carcinogenic properties have been reported. Curcumin treated with CYP2D6 induced DNA damage in the presence of Cu(II). Therefore, curcumin may exhibit carcinogenic potential through oxidative DNA damage by its metabolite.3. Whereas green tea catechins mediate cancer chemopreve … More ntive effects, epidemiological studies indicated positive relationship between green tea consumption and cancer. Catechins induced oxidative DNA damage in human cultured cells. Therefore, oxidative DNA damage may mediate carcinogenesis by catechins.4. Soy isoflavones are representative phytoestrogens that function as cancer chemopreventive agents. However, recent studies indicated that these isoflavones induced cancer of reproductive organs. Our findings suggest that oxidative DNA damage by isoflavone metabolites participates in tumor initiation and that cell proliferation by isoflavones themselves induces tumor promotion.5. we provided an extremely sensitive and specific method to quantify glutathione and other thiols using an electrochemical detector coupled to HPLC with a specially devised gold electrode.6. To examine protein expression by chemopreventive agents, we are performing proteome analysis using peptide mass fingerprinting. In estrogen-sensitive human breast cancer cells, estrogenic compounds increased the expression of VEFG-C, whereas the expression of flotillin-1, hnRNP L and lamin was decreased. Proteome analysis enables to evaluate the safety and effectiveness of chemopreventive agents. Less
抗氧化剂,如蔬菜和水果中所含的维生素和黄酮类化合物,被认为在预防癌症中起着关键作用。然而,流行病学研究表明,b-胡萝卜素增加肺癌的发病率。我们报道了β-胡萝卜素代谢产物诱导DNA氧化损伤。为了建立有效安全的癌症化学预防方法,我们研究了化学预防剂诱导的DNA损伤和基因表达。谷物中所含的植酸可抑制培养细胞中DNA的氧化损伤。植酸本身不会引起DNA损伤。因此,它可能是一种很有前途的癌症化学预防剂.虽然姜黄素具有抗肿瘤活性,但致癌特性已被报道。姜黄素处理与CYP 2D 6诱导DNA损伤的Cu(II)的存在下。因此,姜黄素可能通过其代谢产物氧化损伤DNA而表现出致癌潜力.而绿色茶儿茶素介导癌症的化学预防, ...更多信息 流行病学研究表明,饮用绿色茶与癌症之间存在正相关关系。儿茶素诱导人培养细胞DNA氧化损伤。因此,氧化性DNA损伤可能通过儿茶素介导致癌作用.大豆异黄酮是具有代表性的植物雌激素,可作为癌症化学预防剂发挥作用。然而,最近的研究表明,这些甾体酮诱发生殖器官的癌症。我们的研究结果表明,异黄酮代谢产物对DNA的氧化损伤参与了肿瘤的发生,而异黄酮本身引起的细胞增殖也会促进肿瘤的发生。5.我们提供了一种非常灵敏和特异的方法,使用电化学检测器与具有特殊设计的金电极的HPLC耦合来定量谷胱甘肽和其他硫醇。为了检查化学预防剂的蛋白质表达,我们正在使用肽质量指纹进行蛋白质组分析。在雌激素敏感的人乳腺癌细胞中,雌激素化合物增加VEFG-C的表达,而flotillin-1,hnRNP L和lamin的表达降低。蛋白质组学分析能够评估化学预防剂的安全性和有效性。少
项目成果
期刊论文数量(362)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
及川伸二: "環境因子による酸化的DNA損傷とがん、老化"Environmental Mutagen Research (環境変異原研究). 23. 207-213 (2001)
Shinji Oikawa:“环境因素、癌症和衰老引起的氧化 DNA 损伤”Environmental Mutagen Research 23. 207-213 (2001)。
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Y.Hiraku: "Determination of intracellular glutathione and thiols by high performance liquid chromatography with a gold electrode at the femtomole level : comparison with a spectroscopic assay"Biochim. Biophys. Acta.. 1570. 47-52 (2002)
Y.Hiraku:“通过使用金电极的高效液相色谱法在飞摩尔水平上测定细胞内谷胱甘肽和硫醇:与光谱测定法的比较”Biochim。
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K.Hirakawa: "Base oxidation at 5' site of GG sequence in double-stranded DNA induced by UVA in the presence of xanthone analogues : relationship between the DNA-damaging abilities of photosensitizers and their HOMO energies"Photochem.Photobiol.. 77. 349-3
K.Hirakawa:“在存在氧杂蒽酮类似物的情况下,UVA 诱导双链 DNA GG 序列 5 位点的碱基氧化:光敏剂的 DNA 损伤能力与其 HOMO 能量之间的关系”Photochem.Photobiol.. 77。
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S.Oikawa: "Site-specific hydroxylation at polyguanosine in double-stranded DNA by nickel(II) in the presence of SH compounds : comparison with singlet oxygen-induced DNA damage"Chem.Res.Toxicol.. 15. 1017-1022 (2002)
S.Oikawa:“在 SH 化合物存在下,镍 (II) 对双链 DNA 中的多鸟苷进行位点特异性羟基化:与单线态氧诱导的 DNA 损伤的比较”Chem.Res.Toxicol.. 15. 1017-1022 (
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Y.Hiraku: "Distamycin A, a minor groove binder, changes enediyne-induced DNA cleavage sites and enhances apoptosis"Nucleic Acids Res.. Suppl.2. 95-96 (2002)
Y.Hiraku:“Distamycin A,一种小沟结合物,改变烯二炔诱导的 DNA 切割位点并增强细胞凋亡”Nucleic Acids Res.. Suppl.2。
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KAWANISHI Shosuke其他文献
KAWANISHI Shosuke的其他文献
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{{ truncateString('KAWANISHI Shosuke', 18)}}的其他基金
Molecular epidemiological study on cholangio-carcinogenesis induced by liver fluke Opisthorchis viverrini in Thailand.
泰国肝吸虫 Opisthorchis viverrini 诱发胆管癌的分子流行病学研究。
- 批准号:
21406019 - 财政年份:2009
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Cancer prevention study on the relationship of cancer stem cells biomarker and 8-nitroguanine in cancer tissues
癌组织中癌干细胞生物标志物与8-硝基鸟嘌呤关系的防癌研究
- 批准号:
21390195 - 财政年份:2009
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of the biomarker analysis system for evaluating the risk of carcinogenesis related to infection and inflammation
开发用于评估与感染和炎症相关的致癌风险的生物标志物分析系统
- 批准号:
18390179 - 财政年份:2006
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
The mechanism for the formation of hotspots in relation to evaluation of carcinogenic risks of environmental chemicals
环境化学物质致癌风险评价热点形成机制
- 批准号:
15390187 - 财政年份:2003
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular epidemiological study on the pathogenesis of cholangiocarcinoma caused by infection with liver flukes in Thailand
泰国肝吸虫感染所致胆管癌发病机制的分子流行病学研究
- 批准号:
15406027 - 财政年份:2003
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analysis of sequence-specific DNA damage by oxidative stress and prevention of cancer and aging
分析氧化应激造成的序列特异性 DNA 损伤以及预防癌症和衰老
- 批准号:
12470084 - 财政年份:2000
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Evaluation of toxicity of environmental chemicals on the basis of their estrogenic activity and DNA-damaging ability and regional risk assessment
基于雌激素活性和DNA损伤能力的环境化学品毒性评价和区域风险评估
- 批准号:
11794019 - 财政年份:1999
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for University and Society Collaboration
The method of safety evaluation of chemopreventive agents based on the ability of damaging human genes
基于破坏人体基因能力的化学预防剂安全性评价方法
- 批准号:
10557040 - 财政年份:1998
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
Mechanisms of DNA damage induced by environmental factors and cancer chemoprevention
环境因素诱导的DNA损伤机制与癌症化学预防
- 批准号:
09470101 - 财政年份:1997
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Oxygen radical formation and DNA damage induced by metal compounds in relation to carcinogenicity
金属化合物诱导的氧自由基形成和 DNA 损伤与致癌性的关系
- 批准号:
06454227 - 财政年份:1994
- 资助金额:
$ 9.09万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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Analysis of DNAdamage checkpoint regulator gene and cancer control mechanism in oral cancer
口腔癌DNA损伤检查点调节基因及控癌机制分析
- 批准号:
17591923 - 财政年份:2005
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Grant-in-Aid for Scientific Research (C)
Analysis of meiotic DNAdamage checkpoint
减数分裂 DNA 损伤检查点分析
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14370518 - 财政年份:2002
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$ 9.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)