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氮可引起 DNA 损伤，并在突变和致癌作用中发挥重要作用。我们利用从人类 c-Ha 中获得的 32P 标记 DNA 片段研究了氧化应激介导的 DNA 损伤的序列特异性。 -ras-1、p16 和 p53 基因此外，使用二维凝胶电泳结合质谱分析了经环境因素处理的 HL-60 细胞中的蛋白质表达谱。(1)儿茶酚是一种天然存在的重要工业化学品，已被证明具有很强的促进活性，可诱发啮齿类动物的腺胃肿瘤。此外，儿茶酚是致癌苯的主要代谢物，可诱导HL-60细胞氧化DNA损伤。在存在 Cu(II) 的情况下，儿茶酚会对 32P 标记的 DNA 片段造成损伤。当添加 NADH 时，DNA 损伤明显增强，并且在相对较低浓度的儿茶酚中可以清楚地观察到。 … 更多 ol. 过氧化氢酶抑制 DNA 损伤因此，可以得出结论，儿茶酚通过生成 H2O2 造成的氧化 DNA 损伤在儿茶酚和苯的致癌过程中起着重要作用。此外，环境因素（UVA、苯[a]）。 ]蒽等）、饮食因素（同型半胱氨酸、儿茶素等）以及医疗和药品也会通过 H2O2 的产生诱导序列特异性 DNA 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 代谢物 3-羟基双酚 A (3-OH-BPA) 在 Cu(II) 存在下会引起广泛的 DNA 损伤。 3-OH-BPA 强烈破坏了与 p53 基因突变点 273 号密码子互补的 ACG 序列的 G 和 C。用 BPA 处理的 HL-60 细胞进行了凋亡性死亡，结果显示对照细胞和用 BPA 处理的细胞之间存在四种蛋白质差异表达。这些蛋白质可能与癌发生有关，并且可能作为肿瘤生物标志物。