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

由环境和饮食因素产生的活性氧和氮种可能会导致DNA损伤，并在诱变和致癌作用中起重要作用。我们通过使用从人C-HA-HA-RAS-1，p16和p53基因获得的32p标记的DNA片段研究了氧化应激介导的DNA损伤的序列特异性。此外，使用二维凝胶电泳和质谱法分析了用环境因子处理的HL-60细胞中的蛋白质表达谱。（1）邻苯二酚，自然存在和重要的工业化学化学物质，已被证明具有很强的促进活性并诱导了腺体胃肿瘤，可引起腺体的腺体肿瘤。此外，儿茶酚是致癌苯的主要代谢产物。儿茶酚在HL-60细胞中诱导氧化DNA损伤。在存在Cu（II）的情况下，儿茶酚对32p标记的DNA片段造成损害。当添加NADH时，DNA损伤显着增强，并清楚地观察到相对低浓度的Catechen…更多。过氧化氢酶抑制了DNA损伤。因此，得出的结论是，儿茶酚通过H2O2产生的氧化性DNA损害在儿茶酚和苯的致癌过程中起重要作用（2）在罐头食品和人类唾液中检测到的双酚A（BPA）诱导大鼠的白血病。 BPA代谢产物，3-羟基甲醇A（3-OH-BPA）在Cu（II）和NADH存在下诱导了广泛的DNA损伤。 3-OH-BPA严重损坏了p53基因的突变点的密码子273的ACG序列完整性的G和C。此外，流式细胞仪表明，在凋亡死亡下用BPA处理的HL-60细胞。蛋白质组分析表明，在用BPA处理的对照细胞和细胞之间，四种蛋白质的表达不同。在我们的蛋白质组学研究中鉴定的这些蛋白质可能在癌变中暗示，候选物作为肿瘤生物标志物。较少的