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Analysis of DNA damage by environmental and dietary factors

环境和饮食因素造成的 DNA 损伤分析

基本信息

批准号：
14570298
负责人：
OIKAWA Shinji
金额：
$ 2.11万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570298/
关键词：
dietary factors environmental factors cancer risk assessment reactive oxygen species reactive nitrogen species DNA damage Proteome analysis Carcinogenic mechanism カテキン類ビスフェノールA 食品環境化学物質一酸化窒素紫外線

项目摘要

Reactive oxygen and nitrogen species generated by environmental and dietary factors can cause DNA damage and play important roles in mutagenesis and carcinogenesis. We have investigated sequence specificity of oxidative stress-mediated DNA damage by using 32P-labeled DNA fragments obtained from the human c-Ha-ras-1, p16 and p53 genes. Furthermore, protein expression profile in HL-60 cells treated with an environmental factor was analyzed using two-dimensional gel electrophoresis plus mass spectrometry.(1) Catechol, a naturally occurring and an important industrial chemical, has been shown to have strong promotion activity and induce glandular stomach tumors to rodent. In addition, catechol is a major metabolite of carcinogenic benzene. Catechol induced oxidative DNA damage in HL-60 cells. Catechol caused damage to 32P-Labeled DNA fragments in the presence of Cu(II). When NADH was added, the DNA damage was markedly enhanced and clearly observed of relatively low concentrations of catech … More ol. Catalase inhibited the DNA damage. Therefore, it is concluded that the oxidative DNA damage by catechol through generation of H2O2 plays an important role in the carcinogenic process of catechol and benzene.In addition, environmental factors (UVA, benz[a]anthracene, etc), dietary factors (homocysteine, catechins, etc) and medical and pharmaceutical products also induced sequence-specific DNA damage via H2O2 generation.(2) Bisphenol A (BPA), which has been detected in canned food and human saliva, induced leukemias in rats. A BPA metabolite, 3-hydroxybisphenol A (3-OH-BPA), induced extensive DNA damage in the presence of Cu(II) and NADH. 3-OH-BPA strongly damaged G and C of the ACG sequence complementary to codon 273, a mutational spot of the p53 gene. Furthermore, flow cytometry showed that HL-60 cells treated with BPA underwent apoptotic death. Proteome analysis revealed that four proteins were differentially expressed between control cells and cells treated with BPA. These proteins identified in our proteomic studies may be implicated in carcinogenesis and candidates as tumor biomarkers. Less

环境和饮食因素产生的活性氧和活性氮可引起DNA损伤，在致突变和致癌中起重要作用。我们研究了氧化应激介导的DNA损伤的序列特异性，通过使用32 P标记的DNA片段从人类c-Ha-ras-1，p16和p53基因。此外，蛋白质表达谱分析在HL-60细胞与环境因素处理后，用双向凝胶电泳和质谱。(1)邻苯二酚是一种天然存在的重要化工原料，具有强烈的促癌活性，可诱发啮齿类动物腺胃肿瘤。此外，邻苯二酚是致癌苯的主要代谢产物。邻苯二酚诱导HL-60细胞DNA氧化损伤。邻苯二酚在Cu（II）存在下对32 P标记的DNA片段造成损伤。当加入NADH时，DNA损伤明显增强，并且在相对低浓度的catech中清楚地观察到 ...更多信息 ol.过氧化氢酶抑制DNA损伤。因此，儿茶酚通过产生H2 O2对DNA的氧化损伤在儿茶酚和苯的致癌过程中起重要作用，此外，环境因素（UVA、苯并[a]蒽等）、饮食因素（同型半胱氨酸、儿茶素等）以及医药产品也通过产生H2 O2对DNA产生序列特异性损伤。(2)在罐头食品和人类唾液中检测到的双酚A（BPA）会诱发大鼠白血病。BPA代谢产物3-羟基双酚A（3-OH-BPA）在Cu（II）和NADH存在下诱导广泛的DNA损伤。3-OH-BPA强烈破坏与密码子273互补的ACG序列的G和C，密码子273是p53基因的突变点。此外，流式细胞仪显示BPA处理的HL-60细胞发生凋亡。蛋白质组学分析显示，有四种蛋白质在对照细胞和BPA处理的细胞之间差异表达。在我们的蛋白质组学研究中鉴定的这些蛋白质可能与致癌作用有关，并且可能是肿瘤生物标志物的候选者。少